RACDD 2013 Abstract Book

Index



S.No Topic
1 Speaker Abstracts
2 Content of the participant abstract
3 Abstracts

i. Docking
ii. Docking and Experiment
iii. Pharmacophore, QSAR and Chemoinformatics
iv. Molecular dynamics Simulation and Quantum
mechanics
v. Protein modeling and bioinformatics

























Speaker Abstracts






























Docking and 3D-QSAR studies on the binding of P38 MAP Kinase protease inhibitors

Govardhan A. Balaji, Vitukudi N. Balaji and Shashidhar N. Rao
(Structure Directed Molecular Design, Jubilant Biosys Ltd, #96, Industrial Suburb II Stage, Yeshwantpur,
Bangalore 560 022, India)
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854
Department of Chemistry, St. Joseph College, 36, Langford Road, Bangalore, India 560027


Abstract: We present two separate cross-docking studies on two families of p38 MAP kinase structures
from the protein data bank (PDB) DFG-OUT and non-DFG-OUT. The studies have two main goals: (1) to
determine pose-prediction accuracies of various docking protocols in the cross-docking studies and (2) to
arrive at ensembles of protein structures suitable in reproducing structure-activity relationships (SAR) data
in a few known series of p38 MAP kinase inhibitors. In addition to the docking studies, state-of-the-art
molecular dynamics studies to generate conformational ensembles of the protein structures that address the
SAR of the same series of p38 MAP kinase inhibitors, will be presented. The results of the two approaches
will be useful in identifying MD based protocols in situations where limited X-ray crystallographic data is
available for drug design.





































The Role of Water in Molecular Recognition and Drug Design

Woody Sherman
(Schrdinger Inc., 120 West 45th Street, New York, New York 10036, United States)


Abstract: Water plays a ubiquitous role in biology and forms the foundation for life as we know it. As part
of the protein-ligand binding process, water acts as a direct competitor to ligand binding -- water must be
displaced in order for the ligand to bind. In the process of forming the protein-ligand complex, waters can be
displaced, bridged, buried, perturbed, or completely avoided. Here, describe a method called WaterMap to
assess the thermodynamic characteristics (entropy and enthalpy) of water molecules around proteins and
present applications to kinases, proteases, GPCRs, protein-protein interactions, and other systems.






Computational Drug Design: A Case Study on Xanthine Oxidase Inhibition

Chandrika B-Rao, Smriti Khanna, Vaidehi Korde, Rajiv Sharma, Asha Almeida, Ankita Srivastava,
Kamlesh V Katkar, Usha Ghosh, Sandeep Burudkar, Komal Bajaj, Pranay Shah, Ashish Keche, Anagha
Damre, Prashant Tannu, Nitin J. Deshmukh, Amol Dixit, Yogesh Ahire, Manoja Brahma, Umakant Bahirat,
Lalit Doshi, Kumar V.S. Nemmani, H. Sivaramakrishnan
(Piramal Healthcare Ltd. 1, Nirlon Complex, Next to NSE Complex, Off W.E. Highway, Goregaon(E),
Mumbai 400063, India)


Abstract: In vitro testing for xanthine oxidase inhibition of compounds shortlisted by ligand-based virtual
screening gave 3 hits which shared significant common substructure and had IC50s between 10 and 25 M.
The library compounds were re-synthesized and their in vitro activities confirmed. The isocytosine scaffold
was taken up for structure-based lead generation resulting in over 50 potent compounds with IC50s less than
1 M and 11 compounds with IC50 less than 10 nM. Further lead optimization using iterations of medicinal
chemistry methods, wet-lab results and insights from molecular modeling led to a compound with 10-fold
improvement in in vivo efficacy in an acute hyperuricemic rat model. The entire computation-driven project
was completed in a short span of about 17 months with just 172 compounds being synthesized. The match
between predictions by docking using Glide and in vitro IC50 results was about 72%. The majority of
mismatches were false positives, many of which could be explained by the more rigorous Prime-MM/GBSA
energy calculations of docked structures. This work demonstrated that careful analysis and understanding of
the binding site and ligand-protein interactions, and a judicious combination of different computational
methods, continuously assessed over the course of a drug discovery project using wet-lab data, can provide
more reliable predictions and contribute significantly to speedy discovery of candidate drug molecules.








Insights In To Structure Based Drug Design Through Molecular Modelling - Case Studies

Ramesh Sistla
(Syngene International LTD-BSEZ-S11 Unit II, Biocon Special Economic Zone, Biocon Park, Plot 2&3,
Bommasandra Jigani Link Road, Bangalore, Karnataka, India)


Abstract: Structure based drug design has become a key portfolio in the arsenal of a molecular modeler.
Molecular docking is a very important technique in structure based drug design. It is primarily used to
design compounds that can be reduced to practice in the laboratory. However, intelligent use of this
technique can also give insights into design of other experiments. In this talk, I will give an example of how
docking was used to solve the crystallization problem in case of a protease and enabled rapid lead discovery
using structure based drug design.










































A Quest towards a Robust Small Molecule Docking Algorithm at Peptide-Protein Interface

Samiron Phukan
(Lupin Pharmaceuticals, Lupin Ltd 46/47, A, Village Nande Taluka Muls, Pune 411021, India)


Abstract: Peptide recognition sites of peptide-protein interactions are gaining much attention of late for the
design and discovery of modulators (including allosteric) for many targets of therapeutic importance. Since
many attempts were made to discover such modulators by virtual screening and docking studies, no proper
benchmark is available till date for docking of small molecules at the protein-peptide binding site. In this
context, the present study was undertaken to evaluate the performance of four docking algorithms available
commercially on the peptide-protein interaction region taking a protein-peptide interface as a case study. We
used GLIDE, GRIP, LIBDOCK and LIGAND FIT algorithms to evaluate the docking performance at the
protein-peptide binding site. The findings would be discussed the talk. Although we found different docking
algorithms performed reasonably well in different parameters, we strongly feel the necessity of development
of more robust scoring functions to help in the design and discovery of small molecules functionally
mimicking the peptides of interest.






Modeling and Uncertainties in Protein Design

Y. K. Mathiharan and M. R. N. Murthy
(Molecular Biophysics Unit, Indian Institute of Science, CV Raman Road, Bangalore 560012, India)


Abstract: Domain swapping is an interesting feature of some oligomeric proteins in which each protomer of
the oligomer provides an identical surface for exclusive interaction with a segment or domain belonging to
another protomer. Wild type Salmonella typhimurium survival protein SurE (StSurE) is a dimeric enzyme in
which a large helical segment at the C-terminus and a tetramerization loop comprising two strands are
swapped between the two protomers. Residues H234 and D230 that might promote C-terminal helix
swapping were mutated to alanine. Three-dimensional X-ray crystal structures of the mutants H234A and
D230A/H234A were determined at 2.1 and 2.35 resolutions, respectively. Loss of the crucial D230 OD2
H234 NE2 hydrogen bond (2.89 in the wild type structure) in these mutants lead to large conformational
changes throughout the polypeptide and loss of exact 2-fold molecular symmetry although the oligomeric
form, stabilized by new inter and intra-chain interactions, was retained. Mutants were mostly functionally
inactive, highlighting the importance of precise inter-subunit interactions for the symmetry and function of
StSurE. Comparison of dimeric interface in H234A and D230A/H234A with the wild type StSurE suggested
that a new salt bridge E112 R179 or E112 H180 in these mutants may responsible for the stability of
distorted dimeric organization. With the view of examining additional mutations that may lead to truly
domain unswapped dimers, mutants E112A, E112A/H234A, E112A/D230A, E112A/D230A/H234A,
R179L/H180A/H234A and E112A/R179L/H180A/H234A were constructed. Surprisingly, the native
dimeric structure was restored in these mutants although the site of mutation was far from the hinge
involved in domain swapping. These unexpected results underscore the complexity of protein folding and
suggest that predicting mutational effects could be an uncertain endeavor.


Application of Computational Techniques in Drug Discovery and Exploring New Non-Covalent
Interactions at the Protein-Ligand Interface

Tarun Jain
(Daiichi Sankyo Life Sciences Research Centre India, Plot 20, Sector 18 Gurgaon, Haryana 122001, India)


Abstract: Virtual screening (ligand-based + structure-based), pharmacophore modeling and scaffold-
hopping are some of the important techniques used in computational drug design. These techniques can be
used alone or in combination to provide cost-effective solutions and generate ideas for some of the drug
discovery challenges. Some case studies showing the effective use of these techniques will be presented in
the first part of the talk.
Majority of the ligands bind to protein using non-covalent interactions. Recent research has shown the
existence of a new type of non-covalent interaction called as n* interaction. These interactions are found
in abundance within protein main-chains and have been shown to play an important role in protein structure
formation and stabilization. Second part of the talk will present the study on the identification of n*
interactions at the protein-ligand interface.


Generation of Receptor Structural Ensembles for Virtual Screening Using Binding Site Shape
Analysis and Clustering

Volker Eyrich
(Schrdinger Inc., 120 West 45th Street, New York, New York 10036, United States)


Abstract: In this work, we show that selection of a small set of structures based on clustering on binding
site volume overlaps provides an efficient and effective way to account for protein flexibility in virtual
screening. We first apply the method to crystal structures of cyclin-dependent kinase 2 and HIV protease
and show that virtual screening for ensembles of four cluster representative structures yields consistently
high enrichments and diverse actives. We then apply the method to a structural ensemble of the androgen
receptor generated with molecular dynamics and obtain results that are in agreement with those from the
crystal structures of cyclin-dependent kinase 2 and HIV protease. All the steps will be discussed through a
Knime workflow which will be highlighted during the talk. This work provides a step forward in the
incorporation of protein flexibility into structure-based virtual screening.

References:

David J. Osguthorpe, Woody Sherman, and Arnold T Hagler, J. Phys. Chem. B, 2012, 6952-6959.
David J. Osguthorpe, Woody Sherman, and Arnold T Hagler, Chem. Biol. Drug Design, 2012, 80, 182-193.



Alleviated Drug Discovery with Seurat

Ashish Dugar
(Sphaera Pharma, Plot No. 32, Sector 5, IMT Manesar, Haryana, 122051, INDIA)


Abstract: This will give more insight to researchers, informatics professionals and students on how they can
better focus their efforts in any research activity. How does Seurat help in choosing the right synthetic path?
What is the role that Seurat is capable of playing in the field of drug discovery? Since drug discovery is a
very vast discipline, what are the areas in which one can achieve efficiency and effectiveness by employing
Seurat?


Advances in Molecular Visualization with PyMOL

Jason Vertrees
(Schrdinger Inc., 120 West 45th Street, New York, New York 10036, United States)


Abstract: The visual display of quantitative molecular information plays a central role in modern drug
discovery. Tools that facilitate effective communication of results aid in scientific understanding and
collaboration. In this short demonstration, we will show how PyMOL enables effective communication of
molecular data by quickly creating refined movies and visualizations that can be used to communicate ideas.
Additionally, we will demonstrate new and upcoming features not found in older versions of PyMOL.


Structural Proteome to Targetability Estimation: Novel Concepts in Anti-Infective Discovery

Nagasuma Chandra
(Department of Biochemistry, Indian Institute of Science, CV Raman Road, Bangalore 560012, India)


Abstract: Target identification is a critical step in modern drug discovery. Identifying the right target
however is by no means simple, since a variety of factors need to be considered simultaneously. One of the
main unanswered problems with most clinically used drugs is that many of them exhibit adverse drug effects
due to additional interactions with unintended host proteins. A systems perspective of the proteome in terms
of the interaction profile is essential to understand the pharmacodynamics outcome of a drug. No systematic
method is available at present to address this issue, necessitating development of novel approaches. An ideal
target for an anti-infective drug should first be essential to the pathogen, and preferably also unique, but
should not share similarity in its ability to bind drug-like molecules with proteins from the host. The host
and the pathogen genomes can be compared computationally at various levels of abstractions, such as
through their gene or protein sequences, protein structures; biochemical function(s) and systems level
interactions. Recently, new methods have been developed which enable comparing the host and pathogen
proteomes by identifying the pocketomes in them and their cross comparison. Proteins containing similar
pockets can then be clustered, and a targetability index can be computed. This presents a rational and
systems-level approach to understand drug pharmacodynamics and further to use such knowledge in
discovery of new and safer drugs. A case study with tuberculosis proteome will be discussed.


Rapid and Efficient Development of Acetyl-CoA Carboxylase Inhibitors Using Computational
Techniques

Leah Frye
(Schrdinger Inc., 101 S.W. Main Street, Suite 1300, Portland, OR 97204)


Abstract: Nimbus Discovery is a drug discovery company that uses breakthrough computational approaches
to unlock important, but hard to drug, disease targets. Schrodingers computational chemists and Nimbus
medicinal chemists work closely together to design and test compounds based on Schrdingers structure-
based drug design technology. The development of acetyl-CoA carboxylase (ACC) inhibitors will be
presented to illustrate the power and efficiency of this approach. ACC catalyzes the conversion of acetyl-
CoA to malonyl-CoA, which is an intermediate in the biosynthesis of fatty acids and triglycerides.
Inhibition of ACC reduces fatty acid synthesis and stimulates fatty acid oxidation and has the potential to
favorably affect the morbidity and mortality associated with obesity, diabetes, and fatty liver diseases. Hits
were identified via a structure-based, WaterMap enabled virtual screen against the biotin carboxylase
domain of ACC. The hits were successfully optimized using an iterative approach of compound design
based on enzymatic activity, cellular potency and 3D structures followed by computational evaluation. In
12 months, this process yielded compounds, such as ND-630, with excellent potency and drug-like
properties. In addition, ND-630 has demonstrated in vivo proof-of-concept in pharmacologically relevant
models of target engagement (inhibition of fatty acid synthesis and stimulation of fatty acid oxidation).



Discovery Of Novel Pthalazine Derivatives As Poly(ADP-Ribose)Polymerase (PARP-1) Inhibitors

Jagarlapudi A.R.P. Sarma
(GVK Biosciences Private Limited, Plot No. 28 A, IDA Nacharam, Hyderabad)


Abstract: Poly(ADP-ribose)polymerase (PARP-1) is the nuclear protein, plays an important role in the
DNA repair pathways specifically in the base excision repair pathway. The involvement of PARP-1 in
various therapeutic areas like inflammation, stroke, cardiac ischemia, cancer and diabetes makes it an
important target of research. During the moderate DNA damage, PARP-1 involves in the DNA repair
mechanism and the cell survives and extensive DNA damage, PARP-1 over activation the depletion of
NAD+ and ATP levels further leads to cell death or necrosis. PARP-1 inhibitors in combination with
antitumor drugs are in process of using in cancer chemotherapy and olaparib, veliparib, Iniparib, AG014699,
BMN-673 are clinical candidate pertaining to cancer. In the present study, Analogue and Structure based
models have been used to identify novel PARP-1 inhibitors. A set of 34 compounds were selected for Invitro
biological screening of which 15 compounds showed > 50% inhibition at 20 uM concentration. Five hit
compounds were evaluated for inhibitory concentration. All the five hit compounds possessed the IC50
values < 10 uM. The most potent hit (Pthalazine derivatives, compound 1) showed an inhibitory value of
650 nM towards PARP-1. Further optimization of hit compound 1 is under progress and might be a
promising lead for further research.

References:

1) Satoh MS, Lindahl T. 1992. Role of poly(ADP-ribose) formation in DNA repair. Nature 356: 3568.
2) 2. Golstein P, Kroemer G. 2007. Cell death by necrosis: Towards a molecular definition. Trends
Biochem Sci 32: 37-43.
3) Eliasson M, Sampei K, Mandir AJ. 1997. Poly(ADP-ribose) polymerase gene disrupttion renders mice
resistant to cerebral ischemia. Nat Med 3:1089- 95.
4) Miller MS, Zobre C, Lewis M. 1993. In vitro neuroprotective activity of inhibitors of poly-ADP ribose
polymerase. Soc Neurosci Abstr 19.1656.
5) Pieper AA, Verma A, Zhang J, Snyder SH. 1999. Poly(ADP-ribose) polymerase, nitric oxide and cell
death. Trends Pharmacol Sci 20:171-81.
6) Thiemermann C, Bowes J, Myint FP, Vane JR. 1997. Inhibition of the activity of poly(ADP-ribose)
synthase reduces ischemia-reperfusion injury in the heart and skeletal muscle. Proc Natl Acad Sci USA
94:679-83.
7) Virag L, Szabo C. 2002. The therapeutic potential of Poly(ADPribose) Polymerase inhibitors.
Pharmacol Rev 54:375-429.
8) Tong WM, et al. 2002. Synergistic role of Ku80 and poly (ADP-ribose) Polymerase in suppressing
chromosomal aberrations and liver cancer formation. Cancer Res.62:6990-6.
9) Kim MY, Mauro S, Gevry N, Lis JT, Kraus WL. 2004. NAD-Dependent Modulation of Chromatin
Structure and Transcription by Nucleosome Binding Properties of PARP-1. Cell 119:80314.
10) Kauppinen TM, Swanson RA. 2005. Poly(ADP-ribose) polymerase-1 promotes microglial activation,
proliferation, and matrix metalloproteinase-9-mediated neuron death. J Immunol. 174:2288-96.














Rescued by Protein Models!!!
Kalapatapu V. V. M. Sairam
(Department of Bioinformatics, Zydus Research Center, Sarkhej-Bavla N. H. No. 8A Moriaya, Ahmedabad,
Gujarat 382213)


Abstract: Typically CADD depends on available experimental data for modeling. In my presentation I will
be taking you through few examples where with little information on the protein structure available we
attempted to build models and validate with the help of medicinal chemist.








































FEP/REST for the Calculation of Free Binding Affinities

Jrg Weiser
(Schrdinger Gmbh., Zeppelinstr. 73, 81669 Mnchen, Germany)


Abstract: Accurate and reliable calculation of protein-ligand binding affinities remains a hotbed of
computer-aided drug design research. Despite the potentially large impact FEP (free energy perturbation)
may promise in drug design projects, practical applications of FEP in industrial contexts have been limited
both due to the high computational expense and significant outstanding uncertainties regarding the
underlying accuracy of the method. We here present a recently developed protocol, FEP/REST (free energy
perturbation/replica exchange with solute tempering), and apply this technology to calculate the relative
binding affinities of several sets of congeneric ligands for targets of pharmaceutical interest. We find the
FEP/REST method, when combined with the modern OPLS2.1 force field, provides exceptionally accurate
relative binding affinity predictions, within 1 kcal/mol of the experimental results. Further, we find the
REST enhanced sampling method, when combined with a novel cycle closure error analysis technique,
allows for reliable convergence of up to 6 ligands per day on 12 GPU's.

References:

Lingle Wang,*Yuqing Deng, Jennifer L. Knight, Yujie Wu, Byungchan Kim, Woody Sherman, John C.
Shelley, Teng Lin, and Robert Abel* Modeling Local Structural Rearrangements Using FEP/REST:
Application to Relative Binding Affinity Predictions of CDK2 Inhibitors, J. Chem. Theory Comput.2013, 9,
128212

Prediction of Binding affinities and modes: Authors experience

Vellarkad Vishwanadhan
(Jubilant Biosys Limited, B-34, Sector-58 Noida, U.P-201301, India)


Abstract: The present talk covers examples of Structure-based design (SBDD), homology modeling and
3D-QSAR studies, using Schrodinger tools including Phase, Prime and Glide, and the use of MM-GBSA
methodology for modeling aqueous solvation. These approaches appear to offer a sufficiently physical,
realistic representation of bio-molecular structures and their energetics. The first study reports relatively
high accuracy achieved in binding free energy prediction at a modest computational cost, on a dataset
representing three different targets (Bovine trypsin, human BACE1 and human PDPK-1). The study also
raises questions with regard to approximations involved and the limitations of this approach, which need to
be addressed with explicit modeling of entropy and conformational sampling. Two other studies will be
presented using Prime and Phase tools. These two studies involve 3D-QSAR modeling of over 100
compounds each for human P2X3 and human TRPV1 targets. These studies led to good correlation and
SAR understanding based on congeneric compound structures and their binding affinities. Limitations of the
Phase approaches will be discussed.



Macromodel Conformational analysis for improved prediction of binding modes and free energies

Chandrika Mulakala
(Jubilant Biosys Limited, B-34, Sector-58 Noida, U.P-201301, India)


Abstract: The emerging model of bio molecular recognition is that of conformational selection followed by
induced-fit. The main objective of the talk is to present an approach to address the limitations inherent in
Glide docking as commonly used. This is achieved by the application of conformational selection theory,
which states that binding partners exist in various conformations in solution, with binding involving a
selection among competing conformers. In this talk, we show that a docking protocol designed to mimic
conformational selection in protein-ligand binding significantly enhances cross-docking accuracy over
Glides flexible docking protocol. Our protocol uses an ensemble of ligand conformers pre-generated using
MacroModel, which are then rigidly docked into the active site. Furthermore, we show that the MM-GBSA
flavor of Prime 3.0, VSGB-2.0, with a variable dielectric model and a novel energy function, could be
approaching the accuracy required for evaluating absolute free energies, albeit, through a linear regression
fit. Finally, we show that incorporating a ligand reorganization energy term estimated through
conformational sampling has the potential to further improve the predicted MM-GBSA free energies.


Design, Synthesis and Biological Evaluation of Quinazolinone and Quinazoline Derivatives as -
Glucosidase Inhibitors
Rambabu Gundla
(GVK Biosciences Private Limited, Plot No. 28 A, IDA Nacharam, Hyderabad)


Abstract: Novel quinazolinone and quinazoline based -glucosidase inhibitors have been developed. For
this purpose a virtual screening model has been generated and validated utilizing acarbose as a -glucosidase
inhibitor. Homology modeling, docking, and virtual screening were successfully employed to discover a set
of structurally diverse compounds active against -glucosidase. A search of a 3D database containing 22500
small molecules using the structure based virtual model yielded ten possible candidates. All ten candidates
were N-3-pyridyl-2-cyclopropyl quinazolinone-4-one derivatives, varying at the 6 position. This position
was modified by SuzukiMiyaura cross coupling with aryl, heteroaryl, and alkyl boronic acids. A catalyst
screen was performed, and using the best optimal conditions, a series of twenty five compounds was
synthesized. Notably, the CC cross coupling reactions of the 6-bromo-2-cyclopropyl-3-(pyridyl- 3-
ylmethyl)quinazolin-4(3H)-one precursor have been accomplished at room temperature. A comparison of
the relative reactivities of 6-bromo and 6-chloro-2,3-disubstituted quinazolinones with phenyl boronic acid
was conducted. An investigation of pre-catalyst loading for the reaction of the 6-bromo-2-cyclopropyl- 3-
(pyridyl-3-ylmethyl)quinazolin-4(3H)-one substrate was also carried out. Finally, we submitted our
compounds to biological assays against -glucosidase inhibitors. Of these, three hits (compounds 4a, 4t and
4r) were potentially active as -glucosidase inhibitors and showed activity with IC50 values <20 M. Based
on structural novelty and desirable drug-like properties, 4a was selected for structureactivity relationship
study, and thirteen analogs were synthesized. Nine out of thirteen analogs acted as -glucosidase inhibitors
with IC50 values <10 M. These lead compounds have desirable physicochemical properties and are
excellent candidates for further optimization.






























Design and Discovery of a Novel Glucokinase Activator: Insight from Molecular Modeling Study

Sunil Kumar Panigrahi
(Aurigene Discovery Technologies Limited, 39-40, KIADB Industrial Area, Electronic city Phase II, Hosur
Road, Banglore, Karnataka 560100, India.)


Abstract: Glucokinase (GK) or hexokinase type IV is an enzyme involved in glucose homeostasis and
converts glucose to glucose 6-phosphate in the presence of ATP. GK is predominantly expressed in
pancreatic beta-cells and hepatocytes. It is the rate limiting enzyme for glucose utilization in both liver and
pancreas. It plays a critical role in hepatic glucose metabolism and glycogen synthesis and insulin secretion
in pancreatic cells. In the liver, GK interacts with GKRP (glucokinase regulatory protein) and negatively
regulates GK by reducing its affinity for glucose. GK shows positive co-operativity for glucose and has
sigmoidal kinetics with a Hill coefficient of above 1.5 for glucose. Overall it acts like a glucose sensor and
maintain the normal plasma glucose set point of approximately 5 mM glucose. Therefore, GK activation
serves a therapeutic target for type 2 diabetes. Presence of an allosteric site further enhances druggability of
this target. There are several reports on glucokinase activator (GKA) which binds to this allosteric site.
Herein, we report pyridine class of GKA that activate human pancreatic glucokinase. This was designed
based on pharmacophore model derived from literature compound followed by docking and molecular
dynamics study. Schrodinger suite of software was used to carry all modeling study.




































Finding HITS in Challenging Targets Using SBDD Tools A Continuous Journey

Anil Agarwal
(Integral Biosciences, C-64, Hosiery Complex, Noida Phase-II, Extension, Noida 201306)


Abstract: Scientific advancements during the past two decades have altered the way research produces new
bio-active molecules. In silico techniques such as virtual high throughput screening (VHTS) and de novo
rational structure-based drug design (SBDD) have been established as powerful tools to complement
traditional approaches in drug discovery.
Case studies on the use of various computer-aided drug design (CADD) tools pertaining to two challenging
targets (for which no small molecule inhibitors were reported) will be presented. One of the targets is a
bacterial RNA polymerase (RNAP) for which the only existing drugs in the market are semi-natural
rifamycin group of antibiotics. CADD tools were used to enable the discovery of selective small molecule
inhibitors of bacterial RNAP. Ubiquitin conjugating enzyme (E2) is another challenging target class for
which no inhibitor was reported (except for a specific allosteric inhibitor reported recently)
1
. Using a
combination of various Schrodinger applications helped identify a series of small molecule inhibitors against
this target.

References:

Ceccarelli, D.F., et al. (2011). Cell 145, 10751087.


































Refinement of Protein Structure Homology Models via Long, All-Atom Molecular Dynamics
Simulations

Alpan Raval
(D. E. Shaw Research, New York, New York 10036)


Abstract: Accurate computational prediction of protein structure represents a longstanding challenge in
molecular biology and structure-based drug design. Although homology modeling techniques are widely
used to produce low-resolution models, refining these models to high resolution has proven difficult. With
long enough simulations and sufficiently accurate force fields, molecular dynamics (MD) simulations should
in principle allow such refinement, but efforts to refine homology models using MD have for the most part
yielded disappointing results. It has thus far been unclear whether MD-based refinement is limited primarily
by accessible simulation timescales, force field accuracy, or both. Here, we examine MD as a technique for
homology model refinement using all-atom simulations, each at least 100 microseconds longmore than
100 times longer than previous refinement simulationsand a physics-based force field that was recently
shown to successfully fold a structurally diverse set of fast-folding proteins. In MD simulations of 24
proteins chosen from the refinement category of recent Critical Assessment of Structure Prediction (CASP)
experiments, we find that in most cases, simulations initiated from homology models drift away from the
native structure. Comparison with simulations initiated from the native structure suggests that force field
accuracy is the primary factor limiting MD-based refinement. This problem can be mitigated to some extent
by restricting sampling to the neighborhood of the initial model, leading to structural improvement that,
while limited, is roughly comparable to the leading alternative methods.

























Abstract Contents:

RAACDD No. NAMES
Poster
No. Topics
228 TRILOK DHAN SINGH PQ1
BOMAN INDEX, DRUG LIKE FILTERS AND
MOLECULAR DYNAMICS AS A TOOL IN RATIONAL
DRUG DESIGN: APPLICATION TOWARDS BIOACTIVE
ANALGESIC PEPTIDE LEADS
241 MS JOSHMI JOSEPH D45

Design and Molecular Modelling of Direct Inhibitors of
Mycobacterium Enoyl Co-A Reductase (InhA) as Potential
Antitubercular Agents
700
NAGA SRINIVAS
TRIPURANENI DS28

Design and Synthesis of some novel biologically active 3.5-
disubstituted
1, 2, 4-triazole incorporated 2-mercaptobenzothiazoles
692 sahaj gandhi QM30

Drug Design, Synthesis, Conformational analysis & Docking
studies of Novel Pyrimidine Derivatives: Expected Anticancer
Drugs (Docking, X-ray and DFT Studies)
213 CHINTAMANI JADHAV PQ29

From Natural Product To Natural Product: A Staphylococcus
Aureus NorA Efflux Pump Inhibitors.
129 SUBHRADEEP BHAR BIO4

GENERATION OF 3D MODEL FOR HUMAN CCR5
CHEMOKINE RECEPTOR THROUGH HOMOLOGY
MODELLING AND IDENTIFICATION OF POTENT
INHIBITORS BY MOLECULARDOCKING STUDIES
215
PRATIBHA
PRABHAKARAN DS9

In silico docking analysis of GC-MS derived compounds from
Emilia sonchifolia (L.) DC against Pancreatic cancer
661 P KALAIARASAN QM27

In silico Screening, Activity and Molecular Dynamics
Simulation studies of nsSNPs in Pyruvate Kinase M2
508
S SRI LAVVANY
PRIYA D84

Insights from molecular docking studies of anthocyanins from
Syzygium cumini as potential carbonic anhydrase II inhibitors
for glaucoma.
732 DR M MALLIKA DS31

IN-SILICO DESIGN OF NOVEL SIRT1 INHIBITORS FOR
TARGETING BENIGN PROSTATIC HYPERPLASIA
155 E.PREETHI PQ16

INSILICO STUDIES ON IDENTIFICATION OF ACTIVE
COMPOUNDS FOR GLYCOGEN SYNTHASE KINASE 3-
BETA PROTEIN.
647 HARISH B M DS25

Modeling, Synthesis and Characterization of
Phosphopentapeptide A candidate substrate for Assay of
Calcineurin
660 K SUREKA QM26

Scrutinise of Single Nucleotide Polymorphism (SNPs) in
Human Dihydro Orotate Dehydrogenase (DHODH) through In
silico and to Ascertain Structural Importance
118 Jagatkumar Upadhyay PQ10

Structure Based Subsite Informed Pharmacophore Generation
and its Applications to Virtual Screening of Dipeptidyl
Peptidase IV (DPP-IV) Inhibitors
566 ROOPESH S BIO24
3D computational model of rice bran protease (RBP): First
report of a protease with cupin fold
45
NANDINI SANDEEP
KOTHARKAR PQ2
3D QSAR Study for the development of novel antiretroviral
agents targeting the protease enzymes
683 RAHUL P GANGWAL PQ67
3D-QSAR and molecular docking studies of ureido-substituted
benzene sulfonamides as anti-tubercular agents
242 MS NEENU GANESH PQ33
3D-QSAR study on PA-824 derivatives as antitubercular
agents by Comparative Molecular Similarity Indices Analysis
(CoMSIA)
130 MOHIT JAISWAL PQ12
3D-QSAR, Docking and Pharmacophore modeling of
sulfamates as human Carbonic Anhydrase II (hCA II)
inhibitors
122
K. RAMA
SATYANARAYANA
RAJU BIO35
5-Aminosalicylic acid suppresses crucial cytokines responsible
for aggravating immunological condition in Allergic Asthma
706
SWARUP
CHAKRABARTY D116
A comparative molecular docking analysis on actin aimed to
find its competitive inhibitors in leishmaniasis
71 MR. SAM PAUL D BIO42 A Java based GUI for MOLSDOCK
586 SANDIP WAGHMARE PQ59 A Multifaceted Approach for P-gp Substrate Prediction
134
MS. HARAPRIYA
CHAKRAVARTY DS5
A newer outlook to cardiac arrhythmia: Lead development by
targeting Calsequestrin and its calcium binding
216
PRAVIN VISHNU
SHINDE QM8
A novel role for magnesium in pyrophosphate release and
evidence for a two-metal reaction in N-acetylglucosamine-1-
phosphate Uridyltransferase (GlmU)
406 Fayaz S.M PQ46
A Novel Strategy involving Combined Ligand and Fragment-
based e-Pharmacophores to Identify Novel and Potent RIPK1
Inhibitors
527
JAHEER AHMED
SHAIK D91
A RATIONALE SEARCH OF NEW LEADS FOR ANTI-
TUBERCULAR DRUG DESIGN
229 TEJASHRI DALVI BIO9
A server for classification of human hormones and Non-
hormones based on sequence derived parameters using
artificial neural network
712 D USHARANI QM31
A Single Site mutation (F429H) Converts the Enzyme CYP
2B4 into a Heme Oxygenase: A QM/MM Study
96 T.GANAPATHI D15
Acetyl cholinesterase inhibition of thienopyridines: in silico
and in vivo studies
428 MAHESH HEGDE BIO18
Activation-induced cytidine deaminase: A promising target for
drug designing and therapy
132
DR. PRASHANT S
KHARKAR PQ13
Adventures in Chemical Space: Utility of Constitutional
Isomers in Drug Discovery
178 RAJA REDDY K QM5
Allosteric regulation of pro-apoptotic serine protease HtrA2: a
novel mechanism presenting prospective therapeutic strategies
327
HARISH S
KUNDAIKAR D57
Aminoacid-specific Preferential Binding Site for Ligands A
peptides to Rationalize Drug Design for Alzheimers Disease
509 MR. NIRAJ BABU D85
AN IN SILICO APPROACH TO ANALYZE EPICATECHIN
GALLATE AND ITS DERIVATIVES AS EFFECTIVE
ANTIFIBROTIC AGENTS DURING WOUND HEALING
D.Gunasekaran BIO28
Analysis and identification of -neurotoxin resistant
mechanisms among sensitive and resistant muscle nAChR
Variants
651 S. Divakar D109
Androgen receptor mediated drug development to treat prostate
cancer
299 S NIVEDA PQ37
ANTAGONIZING LuxR DEPENDENT QUORUM
SENSING AND UNDERSTANDING ITS STRUCTURAL
CHANGES:A COMPUTATIONAL APPROACH
752 DR V MADHUMATHI D121
Antimicrobial Activity of Cyanobacteria using In Vitro and In
Silico Analysis
Riddiman BIO27
Application of Homology modeling in Structure based Drug
Discovery: Case study on MELK kinase
57 UPASANA ISSAR D2
Assessment of Molecular Binding of Hoechst 33258
Analogues into DNA Using Docking and MM/GBSA
Approach
322 P PARASURAMAN BIO37
Balancing anti-amyloid and anti-cholinesterase capacity in a
single chemical entity: In-silico drug design
171
DR. MINAKSHI
SONKER QM4 Behavior of biosurfactant, pepfactant liquid-liquid interface
677 SUBRATA DASGUPTA D111
Binding Affinity Based Inhibitor Design for Matrix
Metalloproteinases (MMP-1) by MD-Simulation and Docking
Method
674 ABDULLA AL MASUM D110
Binding of DNA with Rhodamine B: thermodynamic and
molecular modeling studies
272 NABANITA SAIKIA QM11
Carbon based nanostructures as multifunctional platforms for
pyrazinamide drug loading and delivery onto pncA protein - a
molecular dynamics study
49
DEEPAK REDEDY
GADE D1
Chemosensitizing acridones: In vitro calmodulin dependent
cAMP phosphodiesterase inhibition, docking, pharmacophore
modeling and 3D QSAR studies
DEEPAK REDDY GADE D125
Chemosensitizing acridones: In vitro calmodulin dependent
cAMP phosphodiesterase inhibition, docking, pharmacophore
modeling and 3D QSAR studies
Satya Tapas D124
Chorismate synthase from Plasmodium falciparum: A novel
target for anti-malaria drug discovery
164 M.N.S. PAVAN KUMAR PQ18
Combination of Pharmacophore, docking based virtual
screening approaches to identify potential CSF1R inhibitors.
580 S.Mirunalini D128
Combination therapy of 3, 3-Diindolylmethane and 5-
Fluorouracil enhances anticancer activity in human cervical
cancer (HeLa) cell line by inducing apoptosis.
Paramasivan Manivannan PQ76
Comparative genomics of aeruginosins from Microcystis
aeruginosa and Pseudomonas aeruginosa: Insights from T-cell
epitope mapping, 3D-QSAR and docking perspectives with
matrix metalloproteinases.
423 MS. SWAPNA R KALE BIO17
Comparative Pathway Analysis, Homology Modeling, Virtual
screening and ADMET testing to find potential inhibitors
against Aeromonas hydrophila and Pseudomonas aeruginosa
499
MAHESHKUMAR R
BORKAR PQ52
Comparative residue interaction analysis (CoRIA): A 3D-
QSAR study to inspect the thermodynamic events involved in
the binding of Trypanosoma brucei Trypanothione reductase
inhibitors
58 BHARTI BADHAVI D3
Comparative study of inhibition of PDK isozymes with AZ12
and similar inhibitors
331 MR O M DEEPAK D58
COMPREHENSIVE FRAGMENT BASED TECHNIQUE
FOR THE DESIGN OF NOVEL DHFR INHIBITORS
98 A. BHARGAVI PQ9
Computational Approach using Open Source Software: HDAC
Inhibitors for Alzheimer's disease
332 K BHARGAVI D59
COMPUTATIONAL DESIGN AND IDENTIFICATION OF
A NOVEL SQUALENE SYNTHASE INHIBITOR AS
CHOLESTEROL LOWERING AGENT
209 VIKASH KUMAR QM7
Computational insight into interaction of Pkn3 effector domain
with RhoC: A molecular dynamics study and binding free
energy analysis.
377 DR M JACCOB QM14
Computational Modeling of Spin state Dependent Reactivity of
Bio-Inspired Model Complexes of Mononuclear Non-Heme
Enzymes
399 Yamini K BIO15
COMPUTATIONAL MODELLING & ANALYSIS OF
ERBB2 EXPRESSION IN HUMAN GATRIC TISSUES
141 Mahesh Kumar Teli DS6
Computational repurposing and experimental validation of
FDA approved drugs for HIF-Prolyl Hydroxylase inhibition
180 K. KRANTHI RAJ PQ20
Computational strategy to design novel C5-curcuminoids
against cancer
106
RAJESH KUMAR
KESHARWANI D18
Computation-based virtual screening for designing novel anti
breast cancer drugs by targeting Human DNA Topoisomerase
II protein: A structure-based drug designing approach
85 Mr.Surubhotla Raviteja D11
COMPUTER AIDED DESIGN OF LUFFARIELLOLIDE
ANALOGUES FOR TARGETING RETINOIC ACID
RECEPTOR
595
JOSHI HARSHAL
VINODCHANDRA PQ60
COMPUTER AIDED DRUG DESIGNING OF DUAL
INHIBITORS OF AROMATASE (CYP19) AND
ALDOSTERONE SYNTHASE (CYP11B2) FOR
TREATMENT OF BREAST CANCER
550 VAIBHAV JAIN QM22
Conformational Preferences in Nateglinide and Stability of its
Complexation with Dendrimer
187
KHEDKAR VIJAY
MURLIDHAR PQ23
CoRILISA: a novel 3D-QSAR method for comprehending the
thermodynamic events involved in drug-receptor interactions
163
MS. C. LEELA
MADHURI BIO29
Cross talk of AchE inhibitors with Nicotinic Acetylcholine
Receptors
170 ANTARA BANERJEE QM3 Cyclic peptides as molecular transporters and biosurfactants
225 ANANDA. H DS13
Design and Synthesis of new class of ErbB2 inhibitors 4-
thiazolidinones by one pot approach
165
DR. RAVINDRA
KULKARNI PQ19
Design and Synthesis of p38 Kinase inhibitors- A
Computational approach
102 Jay Shah D16
DESIGN OF BENZOTRIAZOLE BASED MULTI-
TARGETED ANTIFUNGAL AGENTS
533 SARADINDU GHOSH PQ54
Design of novel peptidomimetic glucokinase activators for
Type-2 Diabetes using energy based pharmacophore approach
217
DIGAMBAR KUMAR
WAIKER DS10
Design, Synthesis and Biological Evaluation of 6, 7-
Dimethoxy-N-Phenylquinazolin-4-Amine derivatives as Potent
CLK1 Inhibitors
120 AVINEESH SINGH DS2
DESIGN, SYNTHESIS, DOCKING, QSAR STUDIES AND
ANTICANCER EVALUATION OF SOME NOVEL
BENZAMIDE DERIVATIVES AS HISTONE
DEACETYLASE INHIBITORS
79
MUGDHA ROHIT
SURYAWANSHI PQ7
Design, Synthesis, Pharmacological Evaluation and QSAR
studies of benzimidazole compounds as Antidepressant agents.
259 HIMANK KUMAR D48
Design, synthesis, photophysics and DNA damage of
quinolone appended chalcone derivative
282 DINESH KUMAR QM12
Designed isomorphism: A combined experimental and
molecular simulation study
750 DR M MENAKHA BIO30
DESIGNING A COMMON VACCINE CANDIDATE USING
REVERSE VACCINOLOGY FOR MULTIPLE
PATHOGENS CAUSING BACTERIAL ENDOCARDITIS
263 CHETHAN G H D49
DESIGNING OF NOVEL SMALL MOLECULES FOR THE
TREATMENT OF INFLAMMATORY DISEASE: AN IN
SILICO APPROACH
205 REMYA CHANDRAN D36
Designing of novel 7 nicotinic receptor agonists as potential
therapeutic agents for the treatment of cognitive impairments
in Alzheimers disease by core hopping and molecular
modeling methods
63 AJINKYA P SARKATE D5
Designing of Selective TACE Inhibitors: Application of
Induced Fit Docking and Analysis of Active Site By Using
Molecular Docking For Defining the Selectivity of TACE Over
MMPs
373
RAVINDRA
DATTATRAY
WAVHALE DS17
Developing new leads as antitubercular agents that target novel
biological target of Mycobacterium tuberculosis
430
DEEPAK KUMAR
BEHERA PQ47
DEVELOPMENT AND VALIDATION OF
PHARMACOPHORE AND QSAR MODELS FOR
NEURAMINIDASE INHIBITORS
602 TANMAY BANERJEE BIO40
Development of Electronic Notebook (ELN) for chemistry,
using open source tools.
51
PRITAM NAGESH
DUBE PQ3
Development of Energetic Pharmacophore for the designing of
3-phenyl-1-(4-(2-(piperidin-1-yl)ethoxy)phenyl)prop-2-en-1-
one Derivatives as Selective ER- Inhibitors
119 VIJAY KUMAR PATEL PQ11
Development of structure activity correlation model using 3D-
QSAR, pharmacophore and docking studies on thiophene
derivatives as antitumor agent
535 VINOD KUMAR BIO22
Dimerisation of Horsegram Bowman Birk Inhibitor is guided
by an intramolecular interaction in the monomer.
650 DHARSHIT SHAH PQ62
Discovery and evaluation of new leads for competitive
Glycogen Synthase Kinase-3 Inhibitors through
pharmacophore and docking studies
90 K. LEENA D13
DISCOVERY OF SMALL MOLECULE INHIBITORS FOR
AURORA KINASE A USING BOTH LIGAND AND
STRUCTURE BASED DRUG DISCOVERY TECHNIQUE
506 POORNIMA JP D83
Docking and ADME studies on Indole glucosinolates as
Protein-Tyrosine Phosphatase 1B (PTP1B) and Glycogen
synthase kinase -3 (GSK-3) inhibitor against Type 2
diabetes mellitus
526 SHARADDHA JETHI D90
Docking and simulation of ligand molecules of Azadirachta
indica against diabetes
581 J JINO BLESSY D98
Docking studies of C-2/C-5/C-6 modified NeuNac analogues-
Cholera toxin complex
236
MR B
VISHWANATHAN D44
DOCKING STUDIES OF NOVEL HETEROCYCLES
DERIVED FROM BIS 1, 2, 4 TRIAZOLES AGAINST
HUMAN DNA TOPOISOMERASE .
733 G SIVAGAMISUNDARI D117 Docking studies of Pyrimidine derivatives
699 PRAGYA NAYAK D114
DOCKING STUDIES OF SOME NEW THIAZOLIDINONE
DERIVATIVES AS ANTICANCER AGENT WITH
RECEPTOR PROTEIN KINASE INHIBITORS
121 NIROJ SHRESTHA DS3
DOCKING STUDIES OF SOME NOVEL OXAZINE
SUBSTITUTED 9-ANILINO ACRIDINE DERIVATIVES
WITH TOPOISOMERASE II, SYNTHESIS AND
EVALUATION FOR THEIR ANTI-TUMOUR ACTIVITY
690
BAROT
RINKESHKUMAR
ARUJNDBHAI D113
Docking studies of Thiazolidine derivatives using Hex and
Molsoft software
434 Valentina.P D70
Docking Studies on Phytoconstituents of Moringa Olifera as
DNA Gyrase Inhibitors
117
DR. SANJAY P
CHAUHAN D21
Docking study of betalains with HIF prolyl 4-hydroxylase
enzyme
142 PANKAJ WADHWA D25
DOCKING STUDY OF INDOLE DERIVATIVES AS FLAP
ENDONUCLEASE INHIBITOR
70 SANJAY KUMAR DEY DS1
Dopamine--hydroxylase as a novel drug target for
cardiovascular diseases: In silico identification and in vitro
validation of novel inhibitors
502
GAYATRI
RAMAKRISHNAN D81
Employing remote homology detection tools to re-purpose
drugs: A case study with Mycobacterium tuberculosis H37Rv
741
SHABIR AHMAD
GANAI PQ73
Energy optimized pharmacophore approach to identify
potential hotspots during inhibition of Class II HDAC
Isoforms.
221 Kaushik Inamdar D38
E-pharmacophore modeling and docking study based on the
Chikungunya virus nsP23 RNA-binding protein
453 SMRITI KHANNA D72
Explaining in-vitro xanthine oxidase activities of small
molecules using eMBrAcE energies/Computational studies on
papaverine self-association in neutral and acidic conditions
688 SUBRATA PRAMANIK PQ70
Exploring QSTR modeling and toxicophore mapping for
identification of important molecular features contributing to
the chemical toxicity in Escherichia coli
686 PROBIR KUMAR OJHA PQ68
First Report on Exploring Structural Requirements for a Class
of Nucleoside Inhibitors (PfdUTPase) as Antimalarials: QSAR,
Pharmacophore Mapping and Multiple Docking Studies
748 VISHAL PAUL D119
G2PU Accelerated Automated Docking Software With
Integrated Plant Chemical DB as Repository of Ligands: An
Ayurinformatics Approach
577 ABHAYSINH M MORI PQ58
GALAXY Workflow for E-State Index Calculation:
Application in Drug Design
227
MS. HARSHADHA H
PILLEY D42 Ganoderic Acids: potential leads for Cancer
587
AMIT MADHAORAO
PANT D99
High-Throughput Virtual Screening of Pyrimidine Derivatives
Against Alanine Racemase from Streptococcus Pneumoniae
76
SUPRIYA
SRIVASTAVA BIO2
Homology modeling of msp7 like protein in Plasmodium
falciparum A potent target of malaria
175 MONEY GUPTA D30
Homology modeling and docking analysis of RNA chaperone
Hfq in Haemophilus influenzae R2866 involved in
pathogenesis.
162
MR. V. GANESH
KUMAR D29
Homology modeling and docking studies of human 5-HT2C
receptor
511 MS. RITIKA CHAUHAN BIO20
Homology modeling and in silico docking of Trypanothione
reductase of Leishmania donovani for identification of
prospective Antileishmanial drugs
616 K M NOORULLA D103
Homology Modeling and Molecular Docking Studies of MenE
(OSB-CoA Synthase) for Anti-Tubercular Drug Development
466 MRS. V . HYMAVATHI D75
Homology modeling and virtual screening approaches to
identify potent inhibitors of mycolic acid methyltransferase
(Mma1)
468
MR. RAMETENKI
VISHWANATH D76
Homology modeling and Virtual Screening of Ubiquitin
conjugation enzyme RV3 as a novel cancer drug target
53 UZMA KHANAM BIO1
Homology Modeling of Caveolin-1: A Bioinformatics
Approach towards Prostate Cancer Treatment
658 SAPNA RANI BIO26
Homology Modeling of Human CXCR2 Receptor: To
Facilitate Design of Novel Potent Drugs
207 SHARAT CHANDRA BIO8
Homology modeling, docking and molecular dynamic
simulation to gain structural insights of human Sodium-
dependent glucose co-transporter 2 (SGLT2).
514
KAUSHAL KUMAR
SHARMA BIO21
Homology Modelling and Docking study of human analogue
protein ALKBH8 with their inhibitors.
204 DILEEP K V D35
Identification and structure based design of specific CDK5
inhibitors for the treatment of neurodegenerative disorders
125 VIVEK KUMAR SINGH DS4
Identification of Aurora kinase A Selective inhibitor through
Structure-Based Virtual Screening (SBVS)
569 BHARGY SHARMA QM23
Identification of cryptic binding sites of Drp1 using an
integrated computational strategy.
675 DIPIKA RUNGTA QM28
Identification of HIV1 protease inhibitors through molecular
modelling and structure based virtual screening approach
470
MR. RAMAKRISHNA
DUMPATI D77
Identification of novel leads against SOCS protein causing
insulin resistance and type 2 diabetes- A site directed docking
and virtual screening in silico study
388 D. SASIKALA BIO13
Identification of potent inhibitors against FlgT from Vibrio
cholerae by in silico modeling and docking approaches
523
PRASHANT
DESHMUKH DS21
Identification of Potential Inhibitors for Regulating Keap1-
Nrf2 Function
278 JAYADEV JOSHI PQ36
Identification of potential targets for screening and
development of radiation countermeasure agents using
chemoinformatic approaches
485 C. VINODHINI D78
IDENTIFICATION OF SYNTHESISED ANALOGUES OF
SPIROXINDOLE, PYRAZOLE AND PYRROLE AS
POTENTIAL THYMIDYLATE SYNTHASE AND P-
GLYCOPROTEIN INHIBITORS FOR ANTI-CANCER
ACTIVITY BY IN-SILICO DOCKING STUDIES
396 Kunal Zaveriand BIO14
Identification, Structure Prediction and Protein-Protein
Interactions of RNA binding proteins involved in Gene
Silencing Mechanisms of Neurospora crassa
60 TRIPTI KUMARI PQ5
Identifying Novel Antibacterials for Drug-Resistant Strains:
Adopting Ligand and Structure Based Approaches
66 MALKEETH SINGH QM1
Importance of Water Molecules in Determining the Biological
Activity of Ligands: A Case Study of Interleukin-1 Receptor
Associated Kinase (IRAK-4) Inhibitors
531 S. JAYA BHARATHI DS22
IMPROVED SMALL-MOLECULE INHIBITOR OF THE
ZINC ENDOPEPTIDASE OF BOTULINIUM
NEUROTOXIN SEROTYPE A
384 J. PRAJISHA QM16
In - silico studies of PH0702 From Translation Initiation Factor
In Pyrococcus horikoshii OT3
135 TARUN AGARWAL BIO32
In silico analysis of Asparagamine A towards receptor protein
targets in Cancer
554
SUMEET R
DESHMUKH D95
In silico Approach to Construct non mutant Peptide Sequence
for HIV GP 120 and validation confirmed in Docking studies
75 ABHAY KRISHNA D8
In Silico design of drugs for venous thromboembolism and
related cardiovascular diseases
703 MRS ANJANA A K DS30
In silico design, synthesis and Antidiabetic evaluation of some
novel DPP-IV inhibitors
440
RAHUL SHUBHRA
MANDAL DS19
In silico designing and validation of a potential small molecule
inhibitor against AphB, a virulence gene activator from Vibrio
cholerae
487 J. SRIKANTH D79
In silico docking analysis of neuroprotective and cytoprotective
activity of phytoconstituents identified in selected medicinal
plants
279
MEGHANA V
RAYARADDI D129
In Silico drug designing and docking analysis for Alzheimers
disease using Rivastigmine as lead molecule
582 YAMINI CHAND BIO39
In Silico Identification of Potential Drug Targets in Salmonella
enterica serovar Typhi: A Comparative Genomics Study of
Metabolic Pathways
510
MS. SHUMAILA
KHALID D86
In Silico Investigation for Interaction of Hsp90 and Its
Inhibitors
546 S. SANTHIPRIYA QM21
In silico modelling, Dynamics and Docking analysis of Protein
Kinase Epsilon in Bipolar disorder
83 Mr.Barampuram Akhil D10
IN SILICO MOLECULAR MODELING OF
NEURAMINIDASE INHIBITORS AND DOCKING
STUDIES OF ANTI-FLU AGENTS
684 MRS MOHANA K D112
IN SILICO PHYTOCHEMICAL SCREENING FOR THE
INHIBITION OF GLUTATIONE -S TRANSFERASE OF
BRUGIA MALAYI (BmGST) .
230 GEETANJALI THORAT D43
In silico Screening of phyto inhibitors for Human Placental
Aromatase
126 HEMANT ARYA QM2
In silico screening of Traditional Chinese Medicine (TCM)
database to identify leads for Filariasis treatment
59 RICHA ARORA D4
In Silico Study of Active Site of Helicobacter pylori Urease
and its Inhibition by Hydroxamic Acid and its Analogues
426 ROHIT BANSAL QM17
Insights on P-glycoprotein Substrate Binding: Molecular
Dynamics Simulations and In vitro Validation
403 S.GOPINATH D65
INSILICO ANALYSIS OF ALGAL TOXIN INTERACTION
WITH PROTEIN PHOSPHATASE
458 N.GOPINATH D74
Insilico and invitro antimycobacterial screening of 3,4 dihydro
pyrimidones
144 SUBHASH CHANDER PQ14
In-Silico design and study of novel Benzopiperidines as HIV-1
Reverse Transcriptase Inhibitor
350 Tejaswi Bavineni D62 Insilico Discovery of Lead Structures to treat Migraine
89
BINDESH KUMAR
SHUKLA D12
In-silico Docking and Molecular Dynamics Simulation of
Some Pyrazolo[3,4-d]pyrimidine derivatives as antiamoebic
agents
751 DR S VIJAYAKUMAR D120 Insilico drug discovery from Cyanobacteria
232 NIRUPAMA NARAYAN BIO10
Insilico Modeling And Docking Studies On Cytotoxin
Associated Gene A (Caga ) in Helicobacter Pylori
177 MISS. TINKU MONDAL D32
Insilico modification of Some Novel Tetrahydroquinoline
Analogs as Potential Non-Nucleoside Reverse Transcriptase
Inhibitors
488 SINDHUJA D80
In-silico molecular docking studies of quinazolin-4-(3H)- one
derivatives
642 NISHANDHINI M D107 InSilico Screening of Potential Inhibitors against Dengue Virus
72 Hari Om Gupta D54 In-silico stabilization of Microtubule by Taxane Diterpenoids
567 SRUTHI UNNI BIO25
In-silico studies of drug agonists for modelled mutated
Melanocortin4 receptors in the treatment of obesity
568 PRASHANT SAXENA D96
Insilico Studies of Natural LEAD Structures Targeting
Influenza
224 SACHIN HARLE D40
In-silico study of herbal compounds with anti-cancerous
activity
265 MANINDER KAUR PQ34
Integrated Pharmacophore and Docking based Designing of
New Dual Inhibitors of Colony-stimulating Factor-1 Receptor
(cFMS) and Janus Kinase 3 (JAK3)
339 C LOGANATHAN DS16
Investigation on selectivity of novel Beta-Amyloid Precursor
Protein (-APP) inhibitors using chemical feature based
pharmacophore modeling, molecular docking and density
functional theory approaches
105 Dushyant Kumar D17
In-vitro cyclo-oxygenase inhibitory effect of plant extracts and
their fractions
179
RASHMI REKHA
PANIGRAHI QM6
In-vitro meets in-silico: Ligand discrimination by TPR motif in
Toc64 from Arabidopsis thaliana
532 P. CHELLA PERUMAL D92
Isolation of bioactive compound from ethanolic extract of
Cayratia trifolia (L.) against ovarian cancer: A molecular
simulation approach
444
RAJEEV SHARMA
GOPAVAJHALA D71
Kinase inhibitory profiling of lamellarin alkaloids using LPIFD
methodology
238
MR BHARATHKUMAR
INTURI PQ31
Ligand based design, synthesis and CoMSIA studies of new
diphenylamine containing 1,2,4-triazoles as potential anti-TB
agents
745
KANAK
CHAKRABORTY BIO41
LIGAND BINDING STUDIES OF IL6 PROTEIN
RESPONSIBLE FOR RHEUMATOID ARTHRITIS AND
CHEMICAL ANALOGUES OF Vitex negundo
219
SINDHOORA
BHARGAVI G DS11
LIGAND DOCKING AND FRAGMENT-BASED
PHARMACOPHORE BIVARIATE APPROACH FOR
SCREENING OF POTENTIAL DENGUE VIRUS
INHIBITORS
576 PALAK A VYAS D97
Ligand Interactions Profiling in Influenza Neuraminidase-
Antibody Complex: A Study toward Antibody-Drug Conjugate
System
274
M. JANNATHUL
FIRDHOUSE D51
Maestro 9.4 as a tool in the structure based screening of
glycoalkaloids and related compounds, targeting Aldose
reductase
676
DEEPAK KUMAR
MISHRA QM29
MD-Simulation and Docking studies of hIMPDH-IMP analog
complexes: A Step towards the Design of Antileukaemic
Agents.
273 SUKESH KALVA PQ35
MMP-8 inhibition: Combined structure and ligand based
pharmacophore model to identify the potent inhibitors against
rheumatoid arthritis
243 AKSHAY BHATNAGAR D46
Modeling and Docking Studies on Dopamine D2 receptor
protein to identify potent ligands for the treatment of
Parkinsons disease.
168 Sandhaya S BIO6
Modeling of three different conformational states of spo0F
like protein involved in Phosphotransfer Pathway in
MCC0008 (Sample A).
355
DR VEERESH P
VEERAPUR D63
Modulating effect of Embelin and its ninhydrin adducts against
PPAR-g & HMG-CoA: In silico and In vivo studies
632 SHAKTHI DASAN V D105
MOLECULAR DESIGN FOR GLAUCOMA AND NON
INSULIN DEPENDENT DIABETES MELLITUS: A
BETTER LEAD DESIGN BY BINDING FREE ENERGY
CALCULATION
267 SHALINI SINGH D50
Molecular Docking and Dynamic Simulation Study of luteolin
as PDK-1 Kinase Inhibitor
312 SRI SAI MANOHAR D56
MOLECULAR DOCKING APPROACH TO EVALUATING
INHIBITORY ACTIVITY OF CAMPTOTHECIN AND ITS
DERIVATIVES ON DNA- TOPOISOMERASE I.
601 S SHRADDHA D102
Molecular docking based target identification of Curcumin for
Alzheimers disease
147 M. RAMAKRISHNA DS7
Molecular docking guided structure based design of novel
HIV-1 entry inhibitors.
176
MS. SWATI
NILKANTHRAO HADE D31
Molecular docking of Lupeol with Cyclin dependent kinases as
potential anticancer drug target
137 SOMYA ASTHANA D24
Molecular Docking of VEGF receptors with phytochemicals
for the applications in Tissue Engineering
665 ANILKUMAR N DS27
MOLECULAR DOCKING STUDY OF 4-THIAZOLDINONE
DERIVATIVES AS INHIBITORS OF HIV-RT AND
VIRTUAL SCREENING
608 Daniel Yeggoni QM25
Molecular dynamics and Binding studies of Coumarin
Derivatives with Human serum albumin and its biological
significance.
578 SANCHIT BHAKAR QM24
Molecular Dynamics Study of Identified Potential Inhibitors
Leads for PfDHFR Enzyme: Based on 3D Pharmacophore and
Virtual Screening
214 PRIYANKA R SHUKLA D37
Molecular Modeling and Docking of Reverse Transcriptase
and Protease genes with its respective Inhibitors to Evaluate
the Potencies of the HIV Drugs in HIV Drug Resistant Patients
from Western India.
419
PABITRA MOHAN
BEHERA D69
Molecular modeling and identification of glucokinase
activators through molecule docking and molecular dynamics
simulations
594
GAJJAR KRISHNA
ASHOKKUMAR D101
Molecular Modeling Studies of GPCRs involved in Pancreas
Islet Dysfunction
387 C. SATHISHKUMAR BIO12
Molecular modeling, Docking and Molecular dynamics study
of Phospholipase A2 (PLA2)
631 DIVYA PRIYA D104
MOLECULAR MODELLING AND DOCKING ANALYSIS
ON SHRIMP VITELLOGENIN RECEPTOR AND LIGAND
TARGET MEDIATED DELIVERY SYSTEM
198 HEMA GIRISH BIO7
Molecular modelling of the V.cholera LuxO and a virtual
screening studies for the identification of novel inhibitors
556 SHIPRA S RATURI PQ56
Molecular modelling study of PPAR ligands for the
therapeutic application in the treatment of Type-2 diabetes
410
MS. ARCHANA
NAGNATH PANCHE D66
Molecular modelling, virtual screening and docking studies of
the mutants of MECP2 in Rett syndrome
148 DR. L . YAMINI D26
MRCD an aboriginal technique in identification of nearest
native conformation and design of new antifolates towards
ABL kinase
518 ARUN JOHN D87
Multi- faceted utility of in silico tools to explore structure-
function relationships: A case-study of human FASN (Fatty
acid synthase) multi-catalytic domain protein
Dibyabhaba Pradhan D123
Multiple Docking Strategies, Prime/MMGBSA Calculations
and Molecular Dynamics Simulations for Lead Discovery
against Leptospira interrogans
208 SHAGUN KRISHNA PQ28
Multi-Target-Directed Identification for Novel Lead
Candidates against Trypanosoma and Leishmania Glycogen
Synthase Kinase3
521 PUSHPENDRA SINGH D88
Multitargeted molecular docking of plant-derived natural
compounds on receptor tyrosine kinases and androgen receptor
348 R. Krishna Chaitanya D61
NATURAL FLAVANOIDS AS POTENTIAL ALDOSE
REDUCTASE INHIBITORS: A MOLECULAR
MODELLING STUDY
226
LAXMIKANT
DUDHMAL D41
Natural product to natural lead an in silico Fragment based
drug design methodology for Cyclin-dependent kinase 2
inhibitor design.
318 GIJO GEORGE QM13
NMR and Molecular modelling studies of peptide
conformations
417 KEERTHY H K D67
Novel bioactive thiazolidine-4-one small molecules as bacterial
putative target: A Cheminformatic and Bioinformatic
rationalization.
503
S.SUVAITHENAMUDH
AN D82
On the New Inhibitors for the Resistant 5204 Strain of
Penicillin Binding Protein 2B (PBP2B) of Streptococcus
pneumoniae through Structure-Based Virtual Screening
549 FAIZAL P K D94
OPTIMIZATION OF BENZOTHIAZINONES AS
ANTITUBERCULAR AGENT & VIRTUAL SCREENING
OF CHEMICAL DATABASES FOR NOVEL DprE1
INHIBITORS
329
MR ABHIJEET
DHULAP PQ42
Patinformatics as a complimentary tool for the virtual
screening of selective CDK2 inhibitors
603 RAGHAVI SURESH PQ61
PHAMACOPHORE BASED STUDIES ON
IDENTIFICATION OF ACTIVE INHIBITORS FOR
ALZHEIMERS DISEASE
469 MRS. S.P. LAVANYA PQ50
Pharmacophore modeling and virtual screening for protein
tyrosine phosphatase to generate novel inhibitors against
cancer
343 S SANJAY KUMAR PQ43
Pharmacophore based Identification of Inhibitors against RNA
polymerase of Drug Resistant Mycobacterium tuberculosis
323 MONIKA SHARMA PQ40
Pharmacophore Based Virtual Screening for the Identification
of HDAC-6 Selective Inhibitors
218 NIKHIL VIDYASARAR PQ30
Pharmacophore Development for P-Glycoprotein Activators
and Generation of lead from Natural Products for Improved -
amyloid clearance in Alzheimers disease.
555 SHWETA S SONAR PQ55
Pharmacophore Exploration of HIV-1 Protease (PR) Inhibitors
Using Chemometric Techniques
452 BHUMIKA D PATEL PQ48
Pharmacophore Generation and Atom-based 3D-QSAR of 3-
pyridyl Derivatives as DPP-4 Inhibitors.
472
MR. M . KIRAN
KUMAR PQ51
Pharmacophore mapping and 3D QSAR Studies of A1
Adenosine Receptor
505 NABEELA SAYED PQ53
Pharmacophore Mapping Studies To Identify Novel HCV
RNA Polymerase Inhibitors
206 J MOHAN BABU PQ27
Pharmacophore Mapping, 3D QSAR and Docking Studies on
inhibitors of Prolyl oligopeptidase (POP)
81 B.SIVA JYOTHI PQ8
Pharmacophore Modeling and 3D-QSAR Studies on Janus
Kinase-2 Inhibitors
678 KARUNAGARAN S PQ66
Pharmacophore modeling, molecular docking and density
functional theory approaches for identification of novel
Kinesinlike protein 1 (KIF11) inhibitor
156
SIDDHARTH
UPADHYAY PQ17
Pharmacophore Modelling and Docking Simulations Based
Hierarchial Virtual Screening Protocol: Designing of Multi-
Targeted Agents for Interleukin -2-inducible T-cell Kinase
(ITK) and Interleukin-1-Receptor Associated Kinase (IRAK-4)
Inhibitors
747 SANAL DEV PQ75
Pharmacophore modelling, molecular docking and virtual
screening to Identify Novel Topoisomerase-I Inhibitors
657 Shuba Dixit PQ63
Pharmacophore-based 3D-QSAR studies of CCR3 Inhibitors:
A chemical optimization of a potent antagonist for the
treatment of allergic disease
385
KH. DHANACHANDRA
SINGH PQ45
Pharmacophore-based virtual screening and density functional
theory approach to identify dual GPCRs inhibitors
659 MR ANIL K CHINDHE PQ64
PHASE-BASED PHARMACOPHORE MODEL
GENERATION AND 3D-DATABASE SEARCHING FOR
NOVEL AND POTENTIAL 5-HT6 ANTAGONISTS
588 MS J ASNET MARY D127
Polarized docking of Peptide inhibitors on the envelope
glycoprotein of Dengue virus
152
MR RAKESH PANDIT
DHAVALE PQ15
PREDICTING METABOLIC STABILITY AND TOXICITY
OF SOME SMOOTH MUSCLE RELAXANTS
701 PRASANTH FRANCIS D115
Prediction of binding site of Hyrtiocarboline using
computational docking studies
589
MS T MOWNA
SUNDARI D100
PREDICTION OF INTERACTION BETWEEN -
GLUCOSIDASE WITH GANODEROL-B AND
ACARBOSE: AN IN-SILICO APPROACH
328 MIHIR P KHAMBETE PQ41
Prediction of mutagenic potential of nitroaromatics by atom
based QSTR and Density Functional Theory Calculations
687
RUDRA NARAYAN
DAS PQ69
Predictive in silico modeling studies of diverse ionic liquids
towards the inhibition of AChE enzyme of Electrophorus
electricus
246 ARPITHA B M D47
Prioritizing the anticancer properties of curcumin by computer
aided virtual screening and molecular docking
342 ANASUYA DIGHE BIO11
Probing into Protein Binding Sites: A Sequence and Structural
Design Perspective
185 DEBASISH ROY D33
Probing the binding of Syzygium derived -glucosidase
inhibitors with N and C terminal Human Maltase
Glucoamylase by docking and molecular dynamics simulation
484
DR. KATHIRESAN
NATARAJAN QM20
Probing the Conformational Flexibility of Monomeric FtsZ in
GTP-Bound, GDP-Bound, and Nucleotide-Free States
564 NASEEMUSSALAM T K BIO23 Protein Sequence Activity Relationships (ProSAR)
127
TUSHAR DAULATRAO
PATIL D22
Putative target identification against P.aeruginosa by
subtractive genomics approach and In silico drug designing
192 APARNA SHUKLA PQ24
QSAR and docking studies on Capsazepine analogs for
immunomodulatory and anti-inflammatory activity
742 SANDHYA V PQ74
QSAR model for predicting inhibitory activity of COX-2
inhibitors
194 SARFARAZ ALAM PQ25
QSAR modelling, Docking and ADMET studies on Xanthone
derivatives/analogs for Anti-proliferative activity in human
HeLa cancer cell line
239 MR STEPHEN PHILIP PQ32
QSAR STUDIES OF CERTAIN NOVEL HETEROCYCLES
DERIVED FROM BIS- 1, 2, 4 TRIAZOLES AS ANTI-
TUMOR AGENTS.
195 HIMANSHU TRIPATHI PQ26
Quantitative structure activity relationship studies on Eugenol
derivatives/analogs for antifungal activity against Candida
575 Aparna V. Chavan DS24
Quinolines as anticancer agents: The probable candidates for
HDAC inhibition
746 BIJITA BANIK D118
Rational Drug Design For Identifying Novel Target Inhibitors
for Tuberculosis with Components of Asparagus racemosus
183
DR. AMRESH
PRAKASH PQ21
Receptor Chemoprint derived pharmacophore model for
development of CAIX inhibitors
193 POOJA SHARMA D34
ROLE OF CRYSTAL WATER MOLECULES IN DOCKING
STUDIES OF NATURAL INHIBITORS TARGETING
PHOSPHOTIDYLINOSITIDE-3-KINASE (PI3K)
PATHWAY IN CANCER
78 Sai Shashank Chavali D9 Role of Vitamin C as a Collagenase Inhibitor (Human MMP)
559 MINESH A JETHVA PQ57
SAR, Pharmacophore and Molecular Docking Studies of
Aromatase Inhibitors for Therapeutic Application in Post-
menopausal Diseases
525 MANJULA R D89
Screening for the novel potential therapeutic modulators for the
flip form of ionotropic glutamate receptor 2 (iGluA2)
67 SARANYA SIVARAJ D6
Screening of Marine Alkaloids possessing Multi-Target effect
on VEGFR Pathway in Triple Negative Breast Cancer
689 ASHISH NANDY PQ71
Screening of skin sensitization potential of diverse organic
chemicals through the development of classification- and
regression-based QSAR models
457 M SINDHUJA D73
SELECTION OF NOVEL COUMARIN DERIVATIVES AS
HDAC INHIBITORS - AN IN SILICO PREDICTION FOR
CANCER THERAPY
338
S ATHAVAN ALIAS
ANAND D60
Selective Inhibition of TNF-Alpha by Novel Heterocyclic
compounds containing Thiazine Moieties.
74
DAS SOUVIK
PRASANTA D7
SHAPE-BASED DOCKING ANALYSIS OF
PHOSPHORYLATED INSULIN KINASE RECEPTOR
TYROSINE KINASE WITH MUSA SAPEINTUM FLOWER
ALKALOIDS AND FLAVONOIDS
124 S. BALAJI BIO31 Sketching Science with Schrdinger
636 SUGANYA J BIO34
SNP analysis of CAMP-GEFII gene associated with
Polycystic Ovarian Syndrome
113 AYUSH SHRESTHA D20
Soluble epoxide hydrolase inhibitor, t-TUCB, protects against
myocardial ischemic injury in vivo
269
SARAVANAN
MURUGESON QM10
Strategies to identify non-canonical ATP binding sites in
proteins
107 ARAVIND SETTI D19
STRENGTHS AND LIMITATIONS OF PI3K INHIBITORS:
AN INSILICO ANALYSIS/
In silico activity profiling of flavonoids and isoflavonoids in
substrate competitive inhibition of SULT1A1 in breast cancer
306 SHAMBHU MG D55
Structural analysis and lead interaction studies of G72, for
schizophrenia gene
529 MANJULA M BIO38
Structural analysis of ATP-binding subunit of an ABC
transporter from Geobacillus kaustophilus
100 ASHWINI . R BIO3
Structural and Functional Analysis of Butyryl Cholinesterase
Mutants
382 D. PRABHU QM15
Structural and Functional analysis of HEPN protein
(TTHA0427) from Thermus thermophilus HB8 - An
Computational approach
420 PANKAJ KUMAR BIO16
Structural comparison of P-glycoprotein and MRP for substrate
specificity
668 CHANCHAL MONDAL PQ65
Structural findings of cinnolines as anti-schizophrenic
PDE10A inhibitors through comparative chemometric
modeling
456
AWATI PREMA
MAHADEV QM19
STRUCTURAL INSIGHTS OF DNA - PHARMACEUTICAL
BROMINATED IMPURITY COMPLEX
287 MR APPAJI DOKALA DS15
Structural Insights to Target Epidermal Growth Factor
Receptors Dimerization with Novel Small-Molecule Inhibitors
649 SARANYA J D108
Structural, evolutionary and interaction studies of Huntingtin
(HTT), a candidate Huntington protein and its association with
Kalirin
451 SARAH TITUS DS20
Structure based docking assisted identification of 4-
(benzylidene)hydrazinothazoles as novel aurora kinase
inhibitors
157 Swastik Majumdar D28
STRUCTURE BASED DRUG DESIGN OF HYDROXAMIC
ACID, N-HYDROXY-N'-AMINOGUANIDINE
DERIVATIVES AS HDAC8 INHIBITORS AND ITS
DOCKING STUDIES USING MOLECULAR MODELLING
TOOL
223 ARUN KUMAR V A DS12
Structure guided designing of potential lead motifs against
Cancer
186 MANOHAR S PQ22
Structure-Based Design of GRP78 Inhibitors as Novel
Anticancer Agents
131 A.GANDHIMATHI D23
Structure-based virtual screening and evolutionary analysis for
the identification of small molecule inhibitors to abrogate
protein-protein interactions and paracrine Hedgehog Signaling
641
D
ANANTHAKRISHNAN D106
STRUCTURE-BASED VIRTUAL SCREENING
APPROACH TO THE DISCOVERY OF SMALL
MOLECULE INHIBITORS OF HIF- PROLYL
HYDROXYLASE
697 SURYA PRAKASH PQ72
Study of 3D QSAR properties of Semicarbazone as
Anticonvulsant
664 PRIYAM M THAKOR DS26
STUDY OF 4-(ACETYL AMINO)-N-[2-(2,4-
DIMETHOXYPHENYL)-4- OXO-1,3-THIAZOLIDINE-3-
YL] BENZAMIDE AND ITS DERIVATIVES AS POTENT
INHIBITORS OF COX-1: DISCOVERY OF NEW ANTI-
INFLAMATORY DRUGS
433 Keerthana.S.P QM18
STUDY OF DISULFIDE BOND AND DISULFIDE LOOP IN
Cu-Zn SOD1 PROTEIN
Bhadane Rajendra N. D122
STUDY OF NOVEL MESO-SUBSTITUTED PORPHYRINS
AS POTENT G-QUADRUPLEX BINDING TELOMERASE
INHIBITOR USING STRUCTURE BASED DRUG DESIGN
308
PANKAJ KUMAR
SHARMA PQ39
Study of subtype selectivity of human H3 histamine receptor
over H4 histamine receptor using ligand based methods
307 PAKHURI MEHTA PQ38
Study of subtype selectivity of human KCNQ2/Q3 activators
using ligand based methods.
344 SUBHADIP BANERJEE PQ44
Surfing molecular axioms against malaria to find novel
pfDHODH inhibitors utilizing shape similarity fragment
guided virtual screening and chemogenomic analysis
561
MANIKANTA
MURAHARI DS33
Synthesis and Molecular modeling studies of novel acridone
derivatives as P-glycoprotein (P-gp) inhibitors
543 H. BHARATH KUMAR DS23
Synthesis of novel benzoxazine-based aglycones that targets
glycosidases and sodium/glucose cotransporter 1
A. Therasa Alphonsa DS32
Synthesis of Novel Pyrazole derivatives. An investigation on
their ability to inhibit Monoamine Oxidase (MAO)
55
DR. SHANKAR G
ALEGAON PQ4
Synthesis, antitubercular evaluation and field based 3D QSAR
study of pyrazole derivatives
435
SAURABH KUMAR
SINHA DS18
Synthesis, evaluation and molecular docking study of some
new p-aminobenzoic acid derivatives as an antiamnesic and
cognition enhancing agents
271
GHODKE MANGESH
SAKHARAM DS14
Synthesis, In-Vitro, In-Vivo Evaluation And Molecular
Docking Of 2-(3-(2-(1, 3-Dioxoisoindolin-2-Yl) Acetamido)-4-
Oxo-2-Substituted Thiazolidin-5-Yl) Acetic Acid Derivatives
As An Anti-Inflammatory Agents.
702 BINCY BC DS29
Synthesis, Molecular docking, ADMET studies and Cytotoxic
screening of Some Novel Nitrogen Bridge head Heterocycles
Containing 1,2,4-Triazolo[3,4-B](1,3,4)-Thiadiazole Moiety.
172 NITIN MOTILAL ATRE DS8
SYNTHESIS, MOLECULAR DOCKING, AND
EVALUATION OF SOME NOVEL ANALOGUE OF N'-
[SUBSTITUTED]PYRIDINE-4-CARBOHYDRAZIDES AS
POTENTIAL THERAPEUTIC AGENTS
464 PARMAR KAILASH B PQ49
Systematic investigation of cathepsin inhibitors using e-
pharmacophore modelling A structure based approach using
energetic analysis
474 DR. N. NAVANEETHA BIO19
Target specific approach to angiogenesis: Homology
modelling, site specific mutagenesis and virtual screening of a
novel protein kinase
62 Deepak K. Lokwani PQ6
The Prediction of Site of Metabolism (SOM) in ligands,
metabolized by CYP3A4 Enzyme: Comparison of Glide XP
and Induced Fit Docking (IFD)
599 BHARATH B R BIO33
TRAF6 Inhibition: A new paradigm for endotoxin
neutralization
284 KESHAVA M BIO36
Types and number of unique protein fragments that exist in
nature
386 K. GOPINATH D64
Understanding amantadine drug resistance and Identification of
common inhibitors for wild-type and S31N mutant of M2
proton channel
154 K. HARINI D27 Unraveling odor receptor- odor interaction patterns
261
DR VIJAY NARAYAN
MISHRA QM9
Vibrational and Non Linear Analysis Uracil using First
Principle Method
281
CHANDRAKANTH
DEORAM BAGUL D52
Virtual Fragment Screening (VFS) for Epidermal Growth
Factor Receptor
HIMA VYSHNAVI A.M D126
Virtual High Throughput Screening to control the Rice blast
disease caused by Magnaporthe grisea and exploration of
fungicides efficiency
418
A. KRISHNA
CHAITANY D68
Virtual Screening & Molecular Docking Studies of Identified
Potential Drug Targets in Bacillus anthracis
541 POORANI B D93
Virtual Screening of inhibitory Indian phytochemicals against
Human DHODH for Rheumatoid arthritis.
94 CH. NARSAIAH D14
Virtual screening of pyridines targeting tau protein for the
treatment of Alzheimers disease
285
PRATIM
CHAKRABORTY D53 VSTIP: Virtual Screening Tools in Integrated Platform
222 ISHWAR CHANDRA D39
E-Pharmacophore Mapping and Docking Study of NS1 Protein
of Human Influenza A Viruses
145 V. RADHIKA BIO5
Molecular docking guided structure based design of novel
HIV-1 entry inhibitors
754 Shivani Pndey BIO43
Molecular Modeling and functional site prediction of HSP70
protein: Japanese Encephalitis disease






































Docking




















COMPREHENSIVE FRAGMENT BASED TECHNIQUE FOR THE DESIGN OF NOVEL DHFR
INHIBITORS

O M Deepak, Krishnapriya A S, Aparna Nair and Krishnan Namboori P K
Computational Chemistry Group, Computational Engineering and Networking, Amrita Vishwa
Vidyapeetham, Amritanagar, Coimbatore-641112
For correspondence: n_krishnan@cb.amrita.edu
A comprehensive fragment based drug designing strategy has been adopted in this work to identify novel
inhibitors for target DHFR enzyme as promising anti-cancer drugs. In cell cycle, folate is necessary for the
production and maintenance of new cells, for DNA synthesis, RNA synthesis and preventing changes to
DNA [1]. The folate is converted to tetrahydrofolate with the help of DHFR enzyme and the over expression
of the process leads into cancer. Common anti-folate drug, which has been used for years in the treatment of
various cancers such as colorectal and breast cancer is methotrexate. Methotrexate inhibits dihydrofolate
reductase, and thus preventing purine and pyrimidine synthesis, which accounts for its efficacy in the
therapy of cancer as well as for some of its toxicities [2].
In modern drug development, the computer aided drug design (CADD) has been accepted and appreciated as
an essential designing phase. Among various techniques used in CADD, a three dimensional structure based
de novo design strategy has come up as a major leading procedure [3]. The method involves identification
of hotspot or the binding site of the target by Computational Site Identification by Ligand saturation
technique. Then the pharmacophoric or drug template is identified from the hot spot of the target following
FBDD method. By proper scoring and filtering using interaction energy, pharmaco dynamic and pharmaco
kinetic attributes most suitable template has been identified. The template is optimized for all target
molecules by suitable fitting technique [4]. From the optimized and most suitable template, ligand molecules
are generated by evolving the molecule within the binding pocket of the target [5]. The identified ligands are
further evaluated to study their effectiveness in functioning as anticancer drugs by computing ligand
efficiency, fit score, lipophilic efficiency, IC50, and relative enrichment factor. The properties have been
compared with respect to standard anti-cancer drugs. Seven potential leads have been identified, which
exhibit good level of interactions with the target proteins. These selected new ligands help to inhibit the
DNA synthesis and thus leading to the cell to apoptotic pathway, subject to further in vivo and in vitro
evaluation [6].
References
1. Z. Hilal, R. Anwar, K. Omar, and S. Bashar, Cancer Treatment by Greco-Arab and Islamic Herbal
Medicine, The Open Nutraceuticals Journal, vol. 3, pp. 203-212, 2010.
2. A. Alexander and M. Maria, Fragment-Based Drug Discovery: What has it Achieved so Far,
Current Topics in Medicinal Chemistry, vol. 7, pp. 1544-1567, 2007.
3. K. I. Ramachandran, G. Deepa and P. K. Krishnan Namboori, Computational Chemistry and
Molecular Modeling, Principles and Applications Springer, vol. 1, 2008.









DESIGN OF BENZOTRIAZOLE BASED MULTI-TARGETED ANTIFUNGAL AGENTS
Jay Shah, Sachin Malik, Krishnapriya Mohanraj
Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai- 400 098
INTRODUCTION AND OBJECTIVE:
The only target reported for antifungal benzotriazole derivatives is lanosterol 14-alpha demethylase
[1]
,
which is responsible for fungal ergosterol biosynthesis. On design, synthesis and evaluation of certain 1 and
5 substituted benzotriazole derivatives, good correlation between inhibition of ergosterol content and in
silico activity prediction was not observed for some compounds. Hence the possibility of some of these
agents acting on more than one fungal target was investigated, along with standard drug flucanazole. Agents
acting on multiple targets would be useful to combat resistance.
METHODOLOGY:
20 benzotriazole derivatives (1 or 5 substituted) were evaluated using GLIDE docking software on 14 fungal
enzymes, 4 enzymes involved in fungal activity but derived from non-fungal sources, each acting on either
cell wall, cell membrane, nucleus, protein biosynthesis, or vitamin biosynthesis. Also 3 enzymes, involved
in human cholesterol biosynthesis were investigated to rule out toxicity.
RESULTS AND DISCUSSION:
For each enzyme, the docking scores of the test compounds and standard flucanazole were compared with
that of co-crystallized ligand, considering 80% of glide score for co-crystallized ligand in extra precision, as
criteria for activity. It was found that all the 20 compounds showed good GLIDE scores for lanosterol 14-
alpha demethylase. Flucanazole was found to act on 5 more target enzymes, some of them not involved in
ergosterol biosynthesis. Three benzylamine substituted derivatives were found to act on 6 or 7 target
enzymes. Among these, one of them showed activity against human lanosterol 14-alpha demethylase.
CONCLUSION:
Some of the designed benzotriazole derivatives can also inhibit fungal target enzymes other than lanosterol
14-alpha demethylase to show antifungal activity
REFERENCES:
1. Zahra Rezaei et al; European Journal of Medicinal Chemistry, 44, 2009, 30643067
ACKNOWLEDGEMENTS: The authors thank All India Council for Technical Education, New Delhi and
Amrut Modi Research Foundation for providing financial support for this project.









Automated JAVA Based Docking System In Heterogenous High Performance Computing
Environment : An Ayurinformatics Approach
Subrata Sinha*, Deep Jyoti Das, Hemchandra Deka, Vishal Paul*, Mrs.Rashmi Jha, Rabika S. Khati.
Center for Bioinformatics Studies, Dibrugarh University, Dibrugarh-786004, Assam
subratasinha@dibru.ac.in ,vishalll.paulll1703@gmail.com
In the era of modern drug discovery the chemical compounds of medicinal plants, played a major role as a
template for synthesis of new drugs, but only 10-15% of plant chemicals has been so far explored, and so
Insilco drug discovery industries needs to conduct an massive level study on protein-ligands interactions
with plant chemicals as potent ligands for reliable, time efficient and easy selection of ligands based on
traditional knowledge of Ayurveda as well as for designing of new pharmacophore. The major challenges
faced by the industries are the time consuming unreliable phytochemical screening and docking methods.
So, in this paper an attempt has been made to propose a blue-print of a JAVA Based Automated Docking
System integrated with phytochemical, target proteins and ancient knowledge data base in the light of
Ayurveda which is capable of running in high performance heterogeneous computing environment.
Keywords: Automated docking, High performance computing, Ayurinformatics, Heterogeneous
Computing.


















Virtual Fragment Screening (VFS) for Epidermal Growth Factor Receptor
Chandrakant Bagul,
a,b
Ahmed Kamal
a,b *
a
Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology,
Hyderabad, India, 500607

b
Department of Medicinal chemistry, National Institute of Pharmaceutical Education & Research,
Balanagar, Hyderabad, India, 500037
E-mail: ahmedkamal@iict.res.in & bagulc@gmail.com

Now day the major research technique utilized by pharmaceutical industries in drug discovery and lead
development is a screening of huge commercially available compounds against the specific target by
employing High Throughput screening (HTS) Technique. However this technique covered very tiny
chemical space along with very low (0.1%) hit enrichment. Recently Fragment Based Drug Discovery
(FBDD) utilized successfully, where the ligands are built from the well-chosen small fragments that bind
into separate binding pockets. Though the number of fragments screen against the target is small but the
chemical space they covered is more than HTS and hit enrichment is also high (5%). NMR spectroscopy or
X-ray crystallography is being used to identify the binding position of the fragment to receptor. There are
some successful examples for the in silico screening of fragment library.
Recently EGFR has emerged as key and validated target for the development of therapeutics against the
breast cancer and Non-Small Lung Cell Carcinoma (NSLCC), however the cancer cells rapidly acquiring
resistance to leading drugs. With focused to these concern we performed the virtual fragment screening
(VFS) for Epidermal Growth Factor Receptor (EGFR). A fragments library was screened against the EGFR
to get chemically diverse hits which can be a superior starting point for lead development.
References
Chen, Y.; Shoichet, B. K. Nat. chem. Biol. 2009, 5, 358-364.
Huang, D.; Caflisch, A. J. Mol. Recognit. 2010, 23, 183-193.
Warnault, P.; Yasri, A.; Coisy-Quivy, M.; Cheve, G.; Bories, C.; Fauvel, B.; Benhida, R Curr. Med. Chem.
2013, 20, 2043-2067.









E-pharmacophore modeling and docking study based on the Chikungunya virus nsP23 RNA-binding
protein
Kaushik Inamdar, Gayatri Subramanian, Ishwar Chandra, Sarah Cherian*

Bioinformatics Group, National Institute of Virology, Pune 41100, India

Background: Recent outbreaks of the alphavirus, Chikungunya and its resurgence in India after a period of
32 years have added to the need for antivirals. Currently there are no drugs or vaccines available against
Chikungunya. Studies have considered the non-structural protein nsP2 as a potential target for CHIKV
inhibitors
1, 2
. Inspite of these initial efforts, it is imperative to target other viral proteins also. The nsP23
complex of the alpha-viruses is an important part of the replication complex and consists of 4 domains,
namely, protease, zinc binding, macro, and methyl transferase. Recently the structure of the uncleaved nsP23
of Sindbis virus (SINV), another closely related alphavirus, has been elucidated
3
. A putative RNA binding site
was identified near the zinc binding domain in SINV nsP23 complex. Here we explore the CHIKV nsP23-
based RNA binding site based on in-silico strategies using the Schrodinger software suite.
Methodology: The CHIKV nsP23 structure was obtained by homology modeling using SINV nsP23 as a
template and the Prime
4
module. Based on known critical functional residues
3
, the binding site residues in
CHIKV were selected as C1029, C1031, C1033, R1039, R1042, I1052, C1054, and C1072. Energy-
optimized pharmacophore features were generated by docking a fragment library of 441 fragments using
GLIDE
4
module. The pharmacophore hypothesis thus developed was used to screen against the TosLab
database (7000 filtered drug-like compounds) using PHASE
4
.
Results: The pharmacophore model contained two acceptor and two donor features. On the basis of the
screening using this model, 23 compounds were identified as potential ligands for the CHIKV RNA binding
site. 7 compounds with fitness score > 1.0 were docked and 4 of them were found to make contacts with
critical residues. Screening of other compound libraries may further help in identification of other structural
scaffolds and lead compounds that may be tested for antiviral activity.
References:
1. Bassetto et al., (2013), Antiviral Res. Apr; 98(1):12-8.
2. Lucas-Hourani et al., (2013) J Biomol Screen. Feb; 18(2):172-9.
3. Shin et al., (2012), PNAS October 9; 109(41): 1653416539.
4. Prime (Version 3.2), Glide (version 5.9), Phase (version 3.5) Schrdinger, LLC, New York, NY,
2013.




















Novel bioactive thiazolidine-4-one small molecules as bacterial putative target: A Cheminformatic and
Bioinformatic rationalization.
Keerthy H.K.,
a,$
Shardul Paricharak,
b,c,$
Mohan C.D.,
d
Rangappa K.S.,
d
Adriaan P. IJzerman,
c
Andreas
Bender,
b,
and Basappa
a,b,

a
Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Palace Road,
Bangalore-560001, India
b
Unilever Centre for Science Informatics, Department of Chemistry, University of Cambridge,
Lensfield Road, CB2 1EW, Cambridge, United Kingdom
c
Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Leiden
University, P.O. Box 9502, 2300 RA Leiden, The Netherlands
d
Department of Chemistry, University of Mysore, Manasgangotri, Mysore-560001, India

The efficacy of thiazolidine-4-ones as synthons for diverse biological small molecules has given impetus to
antibacterial studies. The newer small thiazolidin-4-one molecules are known to inhibit bacterial type III
secretion, we examined the antibacterial activity of newer thiazolidin-4-ones against two pathogenic strains,
namely, Salmonella typhimurium and Klebsiella pneumoniae. In vitro anti-bacterial studies based on cellular
assays indicated that the compound 3-(benzo[d]isoxazol-3-yl)-2-(3-methoxyphenyl) thiazolidine-4-one
(1a) showed significant inhibitory activity towards Salmonella typhimurium, whose activity is comparable to
gentamicin. In order to rationalise the mode-of-action of the compounds tested, we performed an in-silico
target prediction for the small molecules by applying the Parzen-Rozenblatt Window classifier. As part of
the target prediction, we used a DELTA-BLAST protein domain similarity search to extrapolate from
predicted human targets to homologous targets of Salmonella typhimurium. We identified the novel drug
target DNA translocase FtsK of Salmonella typhimurium for the tested small molecule 1a, which likely
interacts with compound 1a via the FtSK motor domain.
Further, we applied structure based in-silico molecular interaction studies which revealed that compound 1a
interacts strongly with the FtsK motor domain, with a high docking score of 64.6 when compared to other
thiazolidin-4-ones molecules, indicating strong receptor-ligand binding (larger pKi values). In vitro
Salmonella typhimurium bacterial inhibition of compound 1a is correlated with the high dock score against
FTSK motor domain. Therefore, it is likely that compound 1a may disrupt the chromosomal segregation and
thereby inhibit the cell division of Salmonella typhimuriumin culture. Hence, given that both in silico target
prediction, as well as docking studies support the interaction of compound 1a, we present the interaction of
compound 1a with DNA translocase-FtsK as a hypothetical mode-of-action, potentially explaining the
experimentally validated inhibitory activity towards Salmonella typhimurium.







Homology modeling and docking studies of human 5-HT
2C
receptor

Ganesh Kumar.V and Venkateswara Rao Talluri*
Centre for Bioinformatics, Department of Biotechnology, K L University,Vaddeswaram, Guntur District -
522502, AP - India.
Corresponding author email : tvrao_bt@kluniversity.in


5-HT
2C
receptor (5-hydroxytryptamine (serotonin) 2C receptor), a neurotransmitter of GPCR family plays a
major role in the regulation of appetite control and feeding behavior. In the recent times, 5-HT
2C
receptor
has been a focal point as pharmacotherapeutic target for the treatment of obesity. At present, the 3-
diamensional crystal structure information is not available for 5-HT
2C
receptor. In the present work, a
homology model was built based on beta adrenergic receptor template using Prime module of Schrodinger
software suite. The quality of the homology model was evaluated using Ramchandran plot (RAMPAGE)
and 94.9% of amino acid residues are in favorable region, 3.4% residues are in allowed region and 1.7% is
in outliner region. Lorcaserin, an FDA approved drug for obesity was used for docking studies to understand
various receptor-ligand interactions at the active site domain of the model. The overall comparison of 5-
HT
2C
homology model shows a low Root Mean Square Deviation (RMSD) when compared to X-ray
determined structures of similar proteins. It confirms it as a platform for studying the interaction of various
bioactive compounds targeting obesity.

Keywords: 5-HT
2C
, Obesity, Homology modeling, Docking












A comparative molecular docking analysis on actin aimed to find its competitive inhibitors in
leishmaniasis

Swarup Chakrabarty and Koel Mukherjee
Department of Biotechnology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India
835215

Lower Dimer actin (Ld actin), a unique type of eukaryotic actin, different from other actins in terms of its
filament forming. In the study of leishmaniasis, it is of major concern because the infected cells easily
achieve their mobility and hence by infect other cells without being invaded by the macrophages. In this
study, we have docked 30 phytochemicals with anti-trypanosomal and anti-leismanial activity against the
unusual form of actin. As the actin- ATP complex forms a stable structure, we docked our phytochemicals
with the complex as well as actin in the unbound condition and comparative analysis was performed based
on their binding energies. Hydroquinone, Diallyl trisulfide, Gallic acid and Ajoene are found to have a
strong binding affinity for pre-complexed actin molecule. The results could provide the framework for
synthetic modification of bioactive phytochemicals.






















Virtual Screening & Molecular Docking Studies of Identified Potential Drug Targets in
Bacillus anthracis
Amajala Krishna Chaitanya* and Prof. I. Bhaskar Reddy
Department of Biochemistry & Bioinformatics, GITAM Institute of Science, GITAM University, Visakhapatnam
!"##$!, An%hra &ra%esh, In%ia
Email: chy2ak@gmail.com
Anthrax is a naturally occurring infectious disease caused by the spore-forming bacterium Bacillus
anthracis. It is usually seen in wild and domestic mammalian species like cattle, sheep, goats, camels,
antelopes, and other herbivores, but it can also occur in humans when they are exposed to infected animals
or to tissue from infected animals or when anthrax spores are used as a bioterrorist weapon. There were
many documented cases of anthrax since from 1974 all over the world including India. The spore formation
plays a vital role in pathogenicity of the disease, which can last for many years in the soil and have the
ability to survive in adverse conditions. In the cases of infection, drugs like ciprofloxacin or doxycycline
which are common antibiotics are used for the initial therapy. Currently the availability of the vaccine for
the anthrax is also not common to all the humans. Hence in order to address the alternative drugs/vaccine,
here we report some of the key non-human homolog drug targets identified through the in-silico subtractive
genomics approach in which the complete proteome of B. anthracis CDC 684 strain is screened against
databases named human-BLAST and DEG (Database of Essential Genes) and among the identified drug
targets, the PDB ID: 2J13 titled Structure of a family 4 carbohydrate esterase from Bacillus anthracis is
selected for virtual screening & docking process against the Maybridge & Chembridge chemical libraries
using Glide ligand-receptor docking software. The top potential ligands are selected on the basis of visual
inspection & site map field inspection. Further the QM Polarized Ligand Docking (QPLD) is performed for
the best 7 ligands and QPLD scores were computed. The ADMET properties for the selected lead
compounds are predicted using QikProp program of Schrodinger Suite. From the current study, the further
prospective can be directed towards the studies of lead specific pharmacophore modeling and QSAR
studies.
Keywords: Anthrax, Subtractive Genomics, Virtual Screening, Docking, ADMET, CADD










Natural product to natural lead an in-silico Fragment based drug design methodology for Cyclin-
dependent kinase 2 inhibitor design.
Laxmikant Dudhmal*, Nishad Deshpande
CSIR Unit for Research and Development of Information Products "Jopasana", 85/1, Paud Road,
Kothrud Pune -411038. India
Email: laxmikant.dudhmal@urdip.res.in

We describe here, the discovery efforts for novel inhibitors of Cyclin-dependent kinase 2 through fragment-
based drug design approach.In first approach; we use BREED script from Schrodinger, for generation of
novel inhibitors from structures of known ligands bound to a CDK 2 target. In this method, docking of
available natural plant based CDK 2 inhibitors is performed on common target and this ligand-protein bound
structure would be used for designing novel CDK 2 inhibitors. In the process, the ligand-bound target
structures are overlaid, all overlapping bonds in all pairs of ligands are found, and the fragments on each
side of each matching bond are swapped to generate new molecules. As the method is in silico, it can be
applied recursively to generate all possible combinations of known ligands. We thus aim to generate novel
natural plant based ligands using this methodology.
In second approach, database of 1500 plant based natural compounds inhibitors, acting against various
cancer cell lines were generated by searching literature and natural product database resources. These 1500
plant based anticancer agents would be used for generation of fragment library. This fragment library would
further be used for docking studies using Glide software suite of Schrdinger on co-crystal structure of CDK
2 inhibitors. Novel natural plant scaffold or fragment showing binding interaction with active site residue of
targeted protein would be selected for further lead optimization.












Docking & QSAR studies of novel acridone derivatives as Chemosensitizers
Mayur C. Yergeri, Manikanta Murahari, L.B. Nitin
Dept. of Pharmaceutical Chemistry, SVKMs Dr. Bhanuben Nanavati College of Pharmacy, Mumbai,
Maharashtra, India
Multidrug resistance (MDR) of cancer cells is one of the huge challenge and important cause of
chemotherapy failure. Search of new drug to treat MDR cancer is still a challenge for the scientists. An
attempt has been made to evaluate 2,4-dimethylacridones as chemosensitizers. A series of novel 2,4-
dimethyl- N
10
-substituted acridones with alkyl side chain as propyl and butyl, varying tertiary amine groups
at the terminal end of the alkyl side chain have been synthesized and screened against MCF-7, MCF-7/ADR
cells. The compounds have shown good cytotoxicity with an IC
50
of 8-20 M. All the compounds have
shown significant effect on MCF-7/ ADR cells. The aim of this is study is to correlate the biological activity
with the docking scores and to investigate the mode of the interactions at the binding site of P-gp protein,
which might help in further development of potent P-gp inhibitors. Also to develop a QSAR model to
predict the P-gp inhibition activity


















Screening for the novel potential therapeutic modulators for the flip form of ionotropic glutamate
receptor 2 (iGluA2)
Manjula Ramu, Prashant Deshmukh, Balasundaram Padmanabhan
Department of Biophysics, National Institute of Mental Health and Neuroscience (NIMHANS), Bangalore
560 029

AMPA receptors, which mediate the initial peak of excitatory post-synaptic potentials, play critical role in
learning and memory by means of strengthening and weakening of synapses. Positive AMPA modulators
increase glutamate-mediated responses of AMPA receptors by modifying its kinetics (activation,
deactivation and desensitation), conductance, assembly and trafficking. AMPA receptor is a heterotetramer,
composed of four subunits namely GluA1 GluA4. Dysfunction of iGluAs will leads to many neurological
disorders such as ischemia, epilepsy, Alzheimers & Parkinsons diseases, schizophrenia, attention-
deficit/hyperactivity disorder, narcolepsy and autism.
Currently developed compounds such as benzamide derivatives improve normal cognitive function
and cognitive function impaired by aging or schizophrenia. However, these molecules are not effective or
exhibited adverse side effects in animal models or human studies, demonstrating the challenges to discover
compounds that are both effective and tolerated.
Here, we present four new modulators of flip-form of iGluA2 obtained by virtual screening using
NCI-Diversity Set III (Padmanabhan, 2013), as well as preliminary protein production of ligand-binding
domain (LBD) of iGluA2 by refolding process which will subsequently be used for biochemical screening
analysis.

Reference:
Padmanabhan B. Identification of novel modulators for ionotropic glutamate receptor, iGluA2 by in-silico
screening. Theoretical Biology & Medical Modelling. 2013;10:46










Binding of DNA with Rhodamine B: thermodynamic and molecular modeling studies
Md. Maidul Islam
a
*, Maharudra Chakraborty
b
, Prateek Pandya
c
, Abdulla Al Masum
a
, Neelima Gupta
c
,
Subrata Mukhopadhyay
b

a
Department of Chemistry, Aliah University, Sector-V, Salt Lake City, Kolkata 700 091, India
b
Department of Chemistry, Jadavpur University, Kolkata 700 032, India
c
Department of Chemistry, University of Rajasthan, Jaipur, 302 004, India
The affinity of small molecules towards nucleic acids has big potential in study of medicine [1, 2]. The study
of anti-carcinogenic medicines and their interactions with DNA are also significantly important to develop
new cancer therapy treatments [3].
Rhodamine B (RB) is widely used to various biological study [4-5]. It possesses biochemical and
pharmacological effects and shows antibacterial activity upon conjugation with peptides [6]. In our paper
we have studied the binding of Rhodamine B to Calf thymus DNA (CT DNA) using various biophysical
techniques and molecular docking method. From the thermodynamics studies, it was concluded that binding
process is favored by both negative enthalpy change and positive entropy change. Molecular docking
calculations and Quenching experiment confirmed that the dye binds in the minor groove of CT DNA.
These results further advance our knowledge on the molecular aspects on the interaction of these types of
dyes to nucleic acids.
References
[1] Li YQ, Guo YJ, Li XF, Pan JH. Electrochemical studies of the interaction of Basic Brown G with
DNA and determination of DNA.Talanta 2007; 71: 12328.
[2] Hossain M, Suresh Kumar G. DNA intercalation of methylene blue and quinacrine: New insights
into base and sequence specificity from structural and thermodynamic studies with
polynucleotides. Molecular Biosystems 2009; 5: 131122.
[3] Hajian R, TavakolM. Interaction of Anticancer Drug Methotrexate with DS-DNA Analyzed by
Spectroscopic and Electrochemical Methods. E-Journal of Chemistry 2012; 9: 47180.
[4] Karstens T, Kobs K. Rhodamine B and Rhodamine 101 as reference substances for fluorescence
quantum yield measurements. J PhysChem 1980; 84: 187172.
[5] Hasegawa T, Kondo Y, Koizumib Y, Sugiyamab T, Takeda A, Ito S, umio Hamada F. A highly
sensitive probe detecting low pH area of HeLa cells based on RhodamineB modified -
cyclodextrins.Bioorg Med Chem 2009; 17: 601519.
[6] Bucki R, Pastore JJ, Randhawa P, Vegners R, Weiner DJ, Janmey PA. Antibacterial Activities of
Rhodamine B-Conjugated Gelsolin-Derived Peptides Compared to Those of the Antimicrobial
Peptides Cathelicidin LL37, Magainin II, and Melittin, Antimicrobial Agents and Chemotherapy
2004; 48: 152633.







In-silico validation of anti-inflammatory activity of Aurantiamide acetate
Premkumar.G
1
, Muthuramkumar.S
1
, Varatharaju.G
2
, , Mathankumar.V
1
, Balkannan.G
1
, Ramkumar,M
1
. and
Rajrathinam.K
1
*
Department of Botany, V.H.N.Senthikumara Nadar College, Virudhunagar 626 001, Tamilnadu
Depatment of Biotechnology, Nehru Arts and Science College, Coimbtore 641 008, Tamilnadu
*corresponding authors: krrathinam@yahoo.co.in
Aurantiamide acetate is a di-peptide alkaloids. It is a one of the major constituents of Artocarpus
integrefolia, Hybanthus enneaspermus and Moringa oleifera. In the present investigation, molecular
docking studies were performed to validate the anti-inflammatory activity of Aurantiamide acetate against
Cycloxigenase (COX-2). The study revealed the best fitness scores compared with the standard drug
suggesting that it could be effective as the potential inhibitor molecules against COX-2 protein and can be
used as anti-inflammatory drug molecules. .




















In Silico drug designing and docking analysis for Alzheimers disease using Rivastigmine as lead
molecule

Meghana Rayaraddi
1
, Deepak A Yaraguppi
2


1. Student in department of Biotechnology, B.V.Bhoomraddi college of engineering, Hubli.
2. Assistant professor in department of Biotechnology, B.V.Bhoomraddi college of engineering, Hubli.
Alzheimer's disease (AD) is the most common form of dementia, known in medical literature. It is a
degenerative disease i.e it worsens as it progresses, and eventually leads to death. So far, no one single factor
has been identified as a cause for Alzheimer's disease. It is likely that a combination of factors, including
age, genetic inheritance, environmental factors, lifestyle and overall general health, are responsible. Several
competing hypotheses explain the cause of the disease and currently available drug therapies are based on
the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitter
acetylcholine. Studies show that Acetylcholinesterase (AchE )hydrolyzes the neurotransmitter,
acetylcholine at neuromuscular junctions and brain cholinergic synapses, and thus terminates signal
transmission which eventually leads to the disease .Hence protein acetylcholinesterase is selected as
potential target and Rivastigmine appears to be beneficial for people with mild to moderate Alzheimers
diseases which is selected as ligand. 3D structures of protein and ligand are downloaded from Protein data
base (PDB) and are successfully docked using Hex. The binding energies obtained from docking are
analysed. Vibrational analysis is also performed and seven modes of protein are obtained. They are
redocked using Hex software. The best redocked value is -250.3. Redocked value of -250.3 is
comparatively the best fit for acetylcholinesterase enzyme with rivastigmine ligand.






Molecular modelling, virtual screening and docking studies of the mutants of MECP2 in Rett
syndrome
Deepak Pathak*, Vikrant Neware*, Archana Panche*, Manoj Damale*, Sanjay Harke*,
*MGMs Institute of Biosciences and Technology, Mahatma Gandhi Mission, N-6, CIDCO, Aurangabad-
431003, India,
Rett syndrome, a rare neurological disorder primarily occurring in females still has no cure. This disease is
caused by mutations in the gene called Methyl-CpG binding Protein2 (MECP2), located at Xq28 on X
chromosome. The MECP2 protein for the gene MECP2 is a multi-functional protein which regulates the
activity of a host of other genes crucial to normal development. Total 200 mutations pathogenic mutations in
MECP2 have been identified until now, out of which eight mutations are commonly occurring accounting
for almost 70% of all mutations. These common and significant mutations were considered and their protein
structures were modeled using PrimeX tool of Schrodinger. The virtual screening and molecular docking
was performed using Glide tool to obtain the lead candidates for these mutated protein structures. The lead
candidates showing inhibition were tested for ADMET using QuikProp tool of Schrodinger.

















Isolation of bioactive compound from ethanolic extract of Cayratia trifolia (L.) against ovarian cancer:
A molecular simulation approach
P. Chella Perumal
1
, Pratibha Prabhakaran
1,
D.Velmurugan
2
, T.Sivaraman
3
and
V.K. Gopalakrishnan
1
1
Department of Bioinformatics, Karpagam University, Coimbatore, Tamil Nadu-641 021
2
Centre of Advanced Study in Crystallography and Biophysics University of Madras Guindy Campus,
Chennai - 600 025
3
Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA University, Thanjavur,
Tamil Nadu-613401
Cayratia trifolia (L.) is the medicinal plant belongs to the family Vitaceae and its used as diuretic, in
tumors, neuralgia and splenopathy. So far against ovarian cancer, the bioactive compounds have not been
isolated from this plant. Therefore, the purpose of the present study is to isolate and identify the potent anti-
ovarian cancer compounds from the ethanolic extract of Cayratia trifolia (L.) by the steps of fractionation,
purification and structure elucidation is required to characterize the plant based compounds. ADME
properties prediction and molecular docking studies (using QikProp and Glide in Schrodinger Suite) were
conducted to study the molecular interactions of isolated bioactive compound and existing FDA approved
drugs (Cisplatin, Topodecan Hydrochloride, Carboplatin and Cyclophosphamide) with ovarian cancer target
proteins such as HER2, HE4, EGFR and CXCR4, which are frequently over expressed in ovarian cancer.
The crystal form of Epifriedelanol was isolated and identified by X-Ray crystallography method. Further the
molecular docking studies revealed that, Epifriedelanol also has good docking results compared with
existing FDA approved drugs against the target proteins. ADME properties of these compounds were under
the acceptable range. Based on these results this study concluded that, isolated bioactive compound of
Epifriedelanol may act as a good anti-ovarian cancer agent. In future, this compound may lead to novel drug
design and development for ovarian cancer.

Keywords: Cayratia trifolia (L.), X-Ray Crystallography, Epifriedelanol, ADME,Molecular Docking.












IN SILICO PHYTOCHEMICAL SCREENING FOR THE INHIBITION OF GLUTATIONE -S
TRANSFERASE OF BRUGIA MALAYI (BmGST)
Mohana .K and Anant Achary*,
Centre for Research, Department of Biotechnology, Kamaraj College of Engineering and Technology,
Virudhunagar
Email: achyanant@yahoo.com
Glutathione-S transferase is one of the major detoxification enzymes present in filarial worms and play a
role in survival of the parasite in the host. In the present study, structure prediction of monomer of BmGST
was carried out since the experimentally solved structure is not available. Homology modeling was
performed using meta server PMP and the models generated were validated. The best model was chosen.
Homodimer interaction studies were performed in Cluspro server since the active BmGST is a homodimer.
Total number of models predicted was 923. They were clustered into 16 groups based on their root mean
square deviation (RMSD) values and a single representative of each group was obtained. They were
analyzed using structure validation softwares and best model was found out. The Docking studies were
performed using Pyrx. All the molecules were energy minimized with the force field mmff94, conjugate
gradients as an optimization algorithm. Total numbers of steps were set to 200 and the number of step for
update was 1. The substrates Glutathione and the CDNB were docked against the enzyme BmGST and their
molecular interactions were explored. The reported inhibitors such as Ethacrynic acid, Curcumin, Luteolin,
Sulfasalazine, Butein, Quercetin-3 D Glucoside and Triclabendazole were docked against BMGST and
their molecular interactions were studied. This paved way for identification of inhibition strategies of the
enzyme. Potent inhibitors were screened through docking among various groups of phytochemicals such as
phenols, poly phenols, quinines, flavonoids, tannins, coumarins, terpenoids, alkaloids, lectins and saponins.
Several inhibitors were found to selectively bind with the active site. Chebulinic acid was found to be more
potent among them in interacting with the key amino acids that perform the catalysis of the enzyme. Further,
we are carrying out wet lab analysis to test our hypothesis.









Molecular Modeling Studies of GPCRs involved in Pancreas Islet Dysfunction

Ms.Krishna A. Gajjar
1
, Prof.Anuradha K. Gajjar
2

1
Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Post Chandlodia,
Via:Gota, Ahmedabad - 382481.Gujarat
2
Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology,
Changa, Aanand -388421. Gujarat


In 2012, Chemistry Noble Prize has been awarded to the work related to heterotrimeric G protein-coupled
receptors (GPCRs), a large family of signalling proteins which are considered to understand at molecular
level as very few GPCRs have been crystallized so far. Several GPCRs like GPR40 & GPR119 expressed in
the islets of the pancreas are involved in the regulation of islet function and islet hormone secretion, and are
therefore potential targets for treatment of islet dysfunction in type II diabetes. In the course of our research
work, Homology modelling, Molecular docking and pharmacophore generation were performed to explore
the molecular determinants responsible to design the agonists for GPR40 and GPR119. Homology Models
of GPR40 and GPR119 was generated using PRIME module where, crystal structure of bovine rhodopsin
was considered as template. Both the models were further validated using PROCHECK which indicates
more than 95% of the residue angles falling in the favorable regions of Ramachandran plot. These two
Homology models were further used for GLIDE DOCKING of the drug candidates, which are in different
phases of clinical trials. Docking analysis provided the initial idea about important binding requirements for
GPR40 and GPR119. Structure based pharmacophore Models were also generated for both the GPCRs using
PHASE module. Virtual Screening using these pharmacophores and homology models provided a number of
chemical scaffolds and also an insight for the development of selective as well as dual agonists. An attempt
is also made to understand the structural features which resultantly gave deep learning of agonism patterns
(useful in clinical phase of drug discovery) and the selection of drug candidate having long lasting and
desirable pharmacological effect. This approach will be used for designing GPR40 and GPR119 agonists
(dual acting as well), which can be used for the treatment of type II diabetes.












Eugenol Derivatives: A Rational Approach in Computer-Assisted Drug Discovery
Narayan P. Firke
a
, Chetan V. Khachane, Anil G. Markandeya
a

a
Department of Chemistry, Fergusson College, (Affiliated to University of Pune),Pune 411 004, India
Corresponding author: npfirke@gmail.com
Computer-Assisted Drug Discovery has been well developed and successfully applied to the numerous
pharmaceutical targets. However, out of the pool of huge number of drug-like molecules, it is merely a
Hercules task to find out the right lead molecule in course of drug discovery. As a matter of fact, nearly half
of the approved drugs available today are natural product derivatives. In our approach, we herein attempt to
design the lead compound from the Eugenol structure component and 1,2,3-Triazole as scaffold. This
approach has several advantages in improvising lead such as bioavailability, improved binding site, known
metabolites, cumulative effects and synthetic feasibility. The structure-based drug design has now emerged
as one of the powerful tool to verify our hypothesis. The number of structures were sculpted and docked
with 3D crystal structure of Aurora 2 Kinase (PDB-ID: 3LAU), Focal Adhesion Kinase (PDB-ID: 1MP8),
Ephrin receptor A2 (EphA2) (PDB-ID: 1MQ4), Aurora A Kinase (PDB-ID: 4B0G).
Keywords: 2H-1,2,3triazole, 1MP8, 1MQ4, 3LAU, 4B0G, Eugenol.

















Comparative study of inhibition of PDK isozymes with AZ12 and similar inhibitors
Neeta Azad, Bharti Badhani, Rita Kakkar*
*Computational Chemistry Group, Department of Chemistry, University of Delhi, Delhi-110007, India
The Pyruvate Dehydrogenase Complex (PDC) is one of the largest multi-enzyme complexes found in living
cells. In mammals, its activity is regulated by the Pyruvate Dehydrogenase Kinase (PDK) isozymes, which
catalyse the phosphorylation of PDC, causing its inactivation [1,2]. In order to reactivate PDC, an important
target in medical conditions such as heart ischemia and insulin resistant diabetes, several inhibitors of PDKs
have been investigated. These include the potent binding 3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl-
containing inhibitors such as Nov3r, AZ12, and AZD7545. Mammalian PDK exists in four isoforms [3],
each of which displays distinct regulatory properties and tissue distributions [4,5]. Long-term PDK
regulation involves changes in the relative expression of the individual PDK isoforms. We focus on AZ12,
which shows inhibition for all the four isozymes (PDK1, PDK2, PDK3 & PDK4) of the PDK family, though
its docking score is highest for PDK4. In the present work, the inhibiting property of the AZ122 analogues
already studied by us for their PDK2 inhibition [6] have been investigated for the other isozymes of PDK. It
is found that the M41 inhibitor [6], which was found to be the best inhibitor for the PDK2 isozyme, stands at
different positions for the three other members of the PDK family. The docking scores for PDK1, PDK3 and
PDK4 with the M41 inhibitor are found to be -8.5, -7.9 and -4.4, respectively, compared to -13.2 for PDK2.
The inhibiting capacity of the rest of the inhibitors in the considered library is different, but all are found to
inhibit the four isozymes to some extent, as their docking scores are within the inhibiting range.
References
1. Wieland, O. H. (1983) Rev. Physiol. Biochem. Pharmacol. 96: 123-170.
2. Reed, L. J. (2001) J. Biol. Chem. 276: 38329-38336.
3. Gudi, R., Bowker-Kinley, M. M., Kedishvili, N. Y., Zhao, Y. & Popov, K. M.(1995) J. Biol.
Chem. 270: 2898928994.
4. Roche, T. E., Baker, J. C., Yan, X., Hiromasa, Y., Gong, X., Peng, T., Dong, J., Turkan, A. &
Kasten, S.A. (2001) Prog. Nucleic Acid Res. 70: 3375.
5. Sugden, M. C. & Holness, M. J. (2003) Am. J. Physiol. Endocrinol. Metab. 284: 855862.
6. Kakkar, R., Azad, N. & Gahlot, P. (2012) Int. Rev. Biophys. Chem. 5.











AN IN SILICO APPROACH TO ANALYZE EPICATECHIN GALLATE AND ITS
DERIVATIVES AS EFFECTIVE ANTIFIBROTIC AGENTS DURING WOUND HEALING
Dhruva Kumar R, Niraj Babu, B. P. Nayak
Department of Biotechnology and Medical Engineering, NIT Rourkela, Odisha - 769008

The most effective wound treatment is one that minimizes the deposition of unwanted
collagen leading to scar formation succeeding the healing process. Molecular study
of scar formation gives us an insight that the process can be stopped by blocking
the pathway responsible for it. Earlier studies have identified TGF- as the major
player in the pathways leading to scar formation and thus can be targeted for
exploring antifibrotic drugs. The objective of the current study is to search and
validate an effective inhibitor of TGF- receptor by using computational methods
that can act as an antifibrotic agent. A group of newly discovered molecules
obtained from Drug Bank and other natural compounds predicted to act in TGF
pathway were selected to check their inhibitory activity against TGF-1 receptor.
The ligands were docked against the active site of TGF-R1 in Autodock4. Epicatechin
Gallate, a flavonoid, showed highest binding energy (-9.44 kcal/mol) compared to the
control, SB505124 (-9.18 kcal/mol). Since previous studies have confirmed that
Epicatechin Gallate is only effective in minor scars, design of an effective
inhibitor for extensive scar was attempted by modifying the parent structure of
Epicatechin Gallate. A series of ligands thus designed exhibited better binding
energy upon docking. Two such derived ligands (named S1 and S2) showed a binding
energy above -10.4kcal/mol. However, S1 with added hydrophobicity at C5 position
qualified for Drug likeness, Toxicity and ADME properties in PreADMET server. The
same ligand also made a stable complex with the target as obtained in terms of RMSD
and Total Energy measures by real time Molecular Dynamic Simulation studies. All
the studies indicate S1 can act as effective inhibitor of TGF- pathway.
Key Words: TGF-, Drug bank, Docking, Molecular Dynamic Simulation, ADME, PreADMET,
RMSD, Autodock.








Investigation and Docking Studies of Phytochemicals Present in Green Tea, Honey and Cinnamon
against Human Melanocortin-4 Receptor
Vijay ku. Ram, Basant ku. Mehta, Lalit ku. Behera, Payodhar Padhi
Background: Human Melanocortin-4 Receptor (HMC4R) is one of the most potential drug targets for the
treatment of obesity as well as diabetes which controls the appetite. A deletion of the residues 88- 92 in
HMC4R is sometimes the cause of severe obesity in the humans. In this study, homology model has been
constructed for the normal HMC4Rs and mutated HMC4R and some phytochemicals present in Green Tea,
Honey and Cinnamon have been docked to them to study their differential binding to the normal and
mutated HMC4R as compared to the natural agonist - MSH.

Result: Homology model has been constructed for the normal HMC4Rs using the Modeller9v7. Some of the
phytochemicals present in Green Tea, Honey and Cinnamon, which have appetite suppressant activities have
been constructed, minimized and docked to the normal HMC4R model using ArgusLab 4.0.1. Further, the
mode of binding of these phytochemicals with that of the natural agonist - Melanocyte Stimulating
Hormone (-MSH) to normal HMC4Rs have also been studied.

Conclusion: It is observed that the phytochemicals Kaempherol, Epigallocatechin-3-gallate (EGCG) present
in Green Tea and Honey, Isorhamnetin, Chlorogenic acid, Chrysin, Galangin, Pinocambrin present in
Honey, Cinnamaldehyde, Cinnamyl acetate and Cinnamyl alcohol present in Cinnamon have capacity to
form more stable complexes with the normal HMC4R as compared to - MSH. So they are potential
agonists of HMC4R to suppress the appetite.



















Ligand Interactions Profiling in Influenza Neuraminidase-Antibody Complex: A Study toward
Antibody-Drug Conjugate System
Palak A. Vyas, M. Elizabeth Sobhia*
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research
(NIPER), Sector-67, S. A. S. Nagar, Punjab, India
*Email: mesophia@niper.ac.in
Influenza Neuraminidase (NA), a surface glycoprotein, is vital for the propagation of influenza virus and
hence is considered a potential target for the treatment of influenza. Though vaccination is the primary mode
of prophylaxis for this disease, antigenic drifts have made this virus resistant to vaccines. This has widened
the scope for antiviral agents like Zanamivir, Oseltamivir, Peramivir and Laninamivir in the anti-influenza
therapy. Antibodies have also found a significant role against influenza as they bind to the epitope located
on the active site crater. Antibody bound NA showed certain noteworthy conformational changes in the
ligand binding site of the protein when compared to the unbound NA. Studying these conformational
changes with reference to its influence on ligand binding might help in the design of antibody-drug
conjugates which could prove to be more beneficial than the existing therapies. In this study, the existing
marketed drugs were docked into the ligand binding site of NA and
NA-antibody complex separately and subsequently analysed for
significant changes in the interaction profile which could be exploited
for drug designing aimed at influenza treatment.
Key words: Influenza, Neuraminidase, Antibodies, Antiviral agents,
Molecular Docking
References:
1. Colman, P.M. Influenza virus neuraminidase: Structure,
antibodies and inhibitors. Prot. Sci. 1994, 3, 1687-1696.
2. Colmam, P.M.; Laver W.G.; Varghese, J.N. Three
Dimensional structure of complex of antibody with
influenza virus neuraminidase. Nature 1987, 26, 326.
3. Abed, Y.; Boivin, G. Treatment of respiratory virus infections. Antiviral Res. 2006, 70, 1.





















Figure: Crystal Structure of Influenza
Neuraminidase




Biologically important Quinazoline Urea and Thiourea Derivatives

T. Panneer Selvam*
1
, Silveira Karyn Valzita
1
, Arumugam Sivakumar
2

*1
Department of Pharmaceutical Chemistry, PESs Rajaram and Tarabai Bandekar College of Pharmacy,
Faramagudi, Ponda- 403 401, Goa, India
2
School of Bio Sciences and Technology, VIT University, Vellore, Tamilnadu, India

E- Mail address: tpsphc@gmail.com

A series of novel 4-substituted phenyl 3,4,5,6,7,8-hexahydro quinazolin-2-one (1a-l) and 4-substituted
phenyl 3,4,5,6,7,8-hexahydro quinazolin-2-thione (2a-l) with appropriate substituted benzaldehyde. Their
structures were conrmed by IR,
1
H NMR, mass and elemental analyses. These novel quinazoline one
and quinazoline thione derivatives were screened for their in silico study with DNA Gyrase enzyme,
antimicrobial against both Gram-positive and Gram-negative bacteria as well as Fungi and antitubercular
activity against Mycobacterium tuberculosis strain H
37
Rv. In the view of results the most active compounds
carrying thiourea derivatives dominating urea derivatives.

Keywords: Quinazoline, Ones, Thiones, Antibacterial, Antifungal, Antitubercular activities.

















Putative target identification against P.aeruginosa by subtractive genomics approach and In silico
drug designing

Tushar D.Patil & Sanket Darak

Department of Biotechnology, Padmashri Vikhe Patil College of Arts, Science & Commerce, Pravaranagar,
Loni.Maharashtra.
Pseudomonas aeruginosa (UCBPP-PA_14), a gram negative bacterium, is responsible for respiratory, CNS,
ear, eye and urinary tract infections which has developed resistance to antibiotics due to prolong use. Present
work was performed to identify the putative novel targets in Pseudomonas aeruginosa, and in silico drug
designing to identify potential inhibitory molecules that may facilitate the discovery of novel drugs.
The proteome was obtained from UniProt database. To identify paralogus proteins, P.aeruginosa proteome
was analyzed by CDHIT with 60% identity. To find the non-homologous proteins comparison of proteome
of P.aeruginosa and human was done using BLASTP program and 80 proteins were selected. Selected 80
non homologus proteins were analyzed by DEG database to identify critical proteins necessary for survival
of causal organism. KEGG pathway analysis was followed to understand the function of proteins. Posrtb3.0
was used to study subcellular localization, TMHMM analysis was used to identify transmembrane proteins.
Out of 6 transmembrane proteins with vital functions, lnt protein (Apolipoprotein N-acyltransferase) was
selected for homology modeling using Swiss model workspace. Its Binding site was identified by Q site
finder server. Approved drug molecules were retrived from DrugBank to perform virtual screening against
lnt protein using PyRx tool. Ligands with highest score were submitted for protein ligand docking using
Autodock Vina. Bivalirudin showed optimum binding with lnt protein which can lead for drug designing
against pseudomonas aeruginosa.
KEYWORDS- P.aeruginosa, DEG, BLAST, subtractive genomic approach, KEGG, PyRx, Autodock Vina












Prediction of binding site of Hyrtiocarboline using computational docking studies
Prasanth Francis, Dr.M.J.N. Chandrasekar, Anjana.A.K,
Dept. Of Pharmaceutical chemistry, JSS College of pharmacy, Ootacamund, T.N

Hyrtiocarboline, a carboline has been reported to have good antiproliferative activity in H522-TT non-
small cell lung cancer cell line (IC
50
=1.2g/ml), MDA-MB-435 Melanoma (IC
50
=3.0g/ml) and U937
lymphoma cancer cell line (IC
50
=1.5g/ml). Although it has showed good anti-proliferative activity, the
specific antitumor target is not known. In this study we have explored the active site binding mode of
hyrtiocarboline with anti-cancer protein targets like Topoisomerase II, CDK2, CDK4, CDK6, KSP and
Haspin kinase using computational docking programs. Different binding sites were predicted by blind
docking studies, from this study the top ranked binding site were selected based on highest affinity. Induced
fit docking studies were performed based on the binding site predicted by the blind docking studies. The
hydrophobic interaction, hydrogen bonds, Vanderwaals interaction and affinity of protein-hyrtiocarboline
complex were analyzed. Based on the results, we hypothesis that hyrtiocarboline act on multiple targets.
However it was found that of all the targets, hyrtiocarbolines mainly target Haspine kinase and CDK6.






















Computation-based virtual screening for designing novel anti breast cancer drugs by targeting
Human DNA Topoisomerase II protein: A structure-based drug designing approach
Rajesh Kumar Kesharwani, Krishna Misra
Division of Applied Science and Indo-Russian Center for Biotechnology [IRCB], Indian Institute of
Information Technology, Allahabad, India-211012

From recent scientific literature it is evident that curcuminoids play a significant role in combination therapy
of multiple tumors and cancers. However, despite exhaustive work carried out on curcumin no definite drug
profile has so far been obtained. Probably the problem lies with its less bioavailability, poor absorption, and
fast metabolism, efflux from gut and non-selective actions. Moreover, it is not clear whether the therapeutic
activities are due to curcumin alone or due to synergistic action with other curcuminoids. Human DNA
topoisomerases are nuclear enzymes found in all cell types from viruses to human which induce transient
breaks in the DNA giving permission DNA strands or double helices to pass through each other. It is over
expressed in 31% tumors of breast and is almost double in comparison to the normal peripheral blood cells
in case of acute lymphoblastic leukemia. From literature reports it has been found that the action of
curcumin on this conserved nuclear enzyme topoisomerase II leads to poisoning and finally resulting into
the death of the cell, hence, this is a highly important target for breast cancer chemotherapy. The objective
of present study was to design novel potent inhibitors against Human DNA topoisomerase II. Ligbuilder has
been used to design 1000 analogues of curcumin by selecting growing points on the basis of pharmacophore
and key site interaction point on docked conformation of curcumin. For docking and ADME/T prediction we
have used Glide and QikProp respectively supplied with Schrodinger suite. The virtual screening was done
by selecting SP level and then finally XP level docking for getting docked poses with high accuracy. The
simulation results is, 293 analogues showing better binding compared to known inhibitor salvicine and
curcumin itself. The top five analogues have been selected as probable anti breast cancer agents for future
use after in vitro and in vivo evaluation.














Molecular docking based target identification of Curcumin for Alzheimers disease.

Preeti .L, S.Shraddha, T.R.Sambavi, Sujata Roy.
Rajalakshmi Engineering College, Thandalam, Chennai,India.

Curcumin is a polyphenol derived from the rhizome of the plant Curcuma longa, commonly called turmeric.
Curcumin has been extensively studied in modern medicine and Indian systems of medicine for the
treatment of various medical conditions, including cystic fibrosis, haemorrhoids, gastric ulcer, colon cancer,
breast cancer, atherosclerosis, liver diseases and arthritis. It has been used in various types of treatments for
dementia and traumatic brain injury. Along with that Curcumin also has a potential role in the prevention
and treatment of Alzheimer's disease (AD). Though the effect of Curcumin for AD has been studied
experimentally, still the molecular mechanism is unknown. There are many targets identified for AD. Here
we have studied the docking energy of curcumin with five different targets of AD to know where curcumin
is actually binding. We have used Autodock Tools for modeling of curcumin and four different target
proteins. For docking we have used Autodock Vina. We intend to locate the exact binding site and the
molecular mechanism involved in the cure of AD. We have identified whether it has binding potential for
any other targets of Alzheimer's disease, like Acetylcholinesterase, Cholinesterase, Insulin degrading
enzyme, Nitric Oxide Synthase etc. This study would help us synthetically design a drug whose structure
mimics that of curcumin which can be used to treat AD.















Molecular Modeling and Docking of Reverse Transcriptase and Protease genes with its respective
Inhibitors to Evaluate the Potencies of the HIV Drugs in HIV Drug Resistant Patients from Western
India.
Dr. Pravin D. Potdar
1
and Priyanka R.Shukla
2
.
1
Department of Molecular Medicine and Biology, Jaslok Hospital and Research Center, 15 Dr.
G.Deshmukh Marg, Mumbai-400 026, Maharashtra, INDIA
.

2
Department of Bioinformatics,G.N.Khalsa College, Nathalal Parekh Marg, Matunga East, Mumbai-
400019, Maharashtra,INDIA
.
Email Id-shuklapriyanka122@gmail.com.
HIV is a lentivirus (slowly replicating retrovirus) that causes acquired immunodeficiency syndrome
(AIDS), a condition in humans in which progressive failure of the immune system allows life-
threatening opportunistic infections and cancers to thrive. Recently our laboratory has also identified a
novel mutations in RT gene it shows different types of mutations but in different patients. NRTI Resistance
mutations shows M184V,T215G,K219R,T215N which shows very high level of drug resistance to 3TC and
FTC as well as low level of drug resistance to Abacavir (ABC), Didanosine (DDI), Zidovudine (AZT),
Stavudine (D4T) and Tenofovir (TDF). NNRTI Resistance mutations shows Y188L,P225H,M230L,G190A
and F227L which shows very high level of drug resistance to Efavirenz (EFV), Etravirine (ETR), Rilpivirine
(RPV) and Nevirapine (NVP) as well as low level of drug resistance to it. For Protease gene it shows
different types of mutation such as major and minor resistance mutations. In major mutation I84V,G48A and
I54V which shows very high level of drug resistance to Fosamprenavir/r (FPV/r), Nelfinavir (NFV) and
Saquinavir/r (SQV/r) as well as for minor mutation such as Q58E, A71L, G73S, T74P, L76Q, I84T, N88D,
L90P, M46P, I47M, I50N, L76Q, V82G and I84K which shows low level of drug resistance to Atazanavir/r
(ATV/r), Fosamprenavir/r (FPV/r), Saquinavir/r (SQV/r), Tipranavir/r (TPV/r), Indinavir/r (IDV/r),
Lopinavir/r (LPV/r), Nelfinavir (NFV) and Tipranavir/r (TPV/r) .In the present study we have thought of
having In-silico model for confirmation of these drugs which are showing a novel mutation.3D model of
Reverse Transcriptase (RT) and Protease (PR) has been developed and docked with these drugs for
evaluation of their potency. These study further emphasizes that the use of molecular modelling and docking
will have great advantages in evaluation and monitoring drug efficiency before treatment of these drugs in
In-vitro model system.
Keywords: HIV, AIDS, NRTI Resistance, NNRTI Resistance, Reverse Transcriptase gene (RT), Protease
gene (PR), drug resistance.








Multitargeted molecular docking of plant-derived natural compounds on receptor tyrosine kinases and androgen
receptor
Pushpendra Singh, Felix Bast
'entre for Biosciences,

Schoo( of Basic an% App(ie% Science, 'entra( University of &un)a*, Bathin%a, &un)a*, In%ia
+!+##+
Email:pushsingh02@gmail.com
Androgen is the primary growth factor for prostate cancer initiation and progression. However non-
androgenic small peptide growth factors, including insulin, insulin-like growth factor (IGF), epidermal
growth factor (EGF), and vascular endothelial growth factor (VEGF), provide pivotal role for the growth
and regulation of cancer cells. This study is a concerted effort to explore potent and specific multi-targeted
inhibitors against receptor tyrosine kinases and the androgen receptor, employing molecular docking
approach. Non-androgenic receptors such as insulin, insulin-like growth factor receptor (IGFR), epidermal
growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR) and AR were chosen
as protein, and a number of natural compounds from PubChem repository and Updated natural compounds
library (InterBioScreen Ltd) as ligand. Ligands were docked to protein molecules by using Maestro
9.3 (Schrdinger Inc). Docking free energy yielded excellent dock scores for Myricetin and
Epigallocatechin gallate, when docked with proteins AR, EGFR, IR and AR, IGFIR, VEGFIIR, respectively.
Protein-ligand interaction profile highlighted that lipophilic, hydrogen bonding and - stacking interactions
play a pivotal role in protein-ligand interaction at the active site. This study reveals novel classes of natural
compounds that can function as multi-targeted ligands for its possible development in targeted therapeutics.
Information obtained from the current study can prove to be useful to understand protein-ligand interactions
that are required to enhance the cell growth inhibitory activity as well as ADME properties. Further in
vitro and in vivo experimental studies are required for the experimental validation of our findings.
Keywords: ancer! "ndrogen! #eceptor tyrosine kinases! $atural product compounds! %aestro &.'.












Kinase inhibitory profiling of lamellarin alkaloids using LPIFD methodology
Dr. M Murali Krishna Kumar, P. Raghuveer Varma, G. Rajeev Sharma and Sajida Begum
College of Pharmaceutical Sciences, Andhra University, Visakhapatnam
Lamellarin alkaloids are very interesting secondary metabolites derived from phenyl alanine or tyrosine
based biosynthesis, reported from several marine invertebrates including ascidians, sponges and cnidarians.
These molecules are recognized by their unique substitution pattern observed around a pyrrole, with 3,4
diaryl substitution with nitrogen of the pyrrole substituted with aryl ethyl moiety. A combination of aryl
substitutions including intramolecular reactions resulted in over 200 molecules reported so far. Very
interesting part of the research is their bioactivity pattern. Lamellarins and related molecules were reported
to possess antibiotic, anticancer, enzyme inhibitory and anti-inflammatory activities. An interesting and
closely related compound Staurosporine, which is first of its kind in kinase enzyme inhibitory pattern,
started looking into related molecules to probe for selective kinase enzyme inhibition, with potential
applications in anticancer, anti-inflammatory and autoimmune disorders. With this backdrop, we wish to
perform Ligand Protein Inverse Fit Docking protocol involving a database of 220 lamellarins against 135
kinase enzymes (structures available online) to analyze their binding to arrive at their possible mechanism of
action and also to propose new lead molecules for the respective kinases.




















STUDY OF NOVEL MESO-SUBSTITUTED PORPHYRINS AS POTENT G-QUADRUPLEX
BINDING TELOMERASE INHIBITOR USING STRUCTURE BASED DRUG DESIGN
Rajendra Bhadane
*
, Rupali Bhadane

, Dhananjay Meshram
#

*Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Mahal, Jaipur, Rajasthan, India.

Loknete Dr. J. D. Pawar College of Pharmacy, A/P-Manur, Tal-Kalwan, Dist-Nashik, Maharashtra, India.
#
Pioneer Pharmacy Degree College, Sayajipura, Ajwa-Nimeta Road, Vadodara, Gujarat, India.

The biological significance of G-quadruplex has been recognized by numerous research efforts. With the
advancement of x-ray crystallography, CD and NMR spectroscopy studies, the structure and topology of G-
quadruplex has become clear than before. As there are many G-rich regions along chromosomes and some
of these are associated with the promoter of oncogenes. This provided us an excellent opportunity to
perform structure based drug design to target telomeric and oncogene promoter sequences using series of
meso- substituted porphyrins. In the proposed research work ligand based docking was carried out on
Schrdinger 2011 suite using maestro elements. The docking was carried out on two oncogene promoter
sequences with PDB id 2A5R and 2HRI. Among the number of inhibitors four legends shows promising
binding ability in comparison with known inhibitor of G-quadruplex TMPyP4.
Keywords: Telomerase, G-quadruplex

















STUDY OF NOVEL MESO-SUBSTITUTED PORPHYRINS AS POTENT G-QUADRUPLEX
BINDING TELOMERASE INHIBITOR USING STRUCTURE BASED DRUG DESIGN
Rajendra Bhadane
*
, Rupali Bhadane

, Avish Maru

, Dhananjay Meshram
#

*Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Mahal, Jaipur, Rajasthan, India.

Loknete Dr. J. D. Pawar College of Pharmacy, A/P-Manur, Tal-Kalwan, Dist-Nashik, Maharashtra, India.
#
Pioneer Pharmacy Degree College, Sayajipura, Ajwa-Nimeta Road, Vadodara, Gujarat, India.

The biological significance of G-quadruplex has been recognized by numerous research efforts. With the
advancement of x-ray crystallography, CD and NMR spectroscopy studies, the structure and topology of G-
quadruplex has become clear than before. As there are many G-rich regions along chromosomes and some
of these are associated with the promoter of oncogenes. This provided us an excellent opportunity to
perform structure based drug design to target telomeric and oncogenes promoter sequences of 2A5R and
2HRI quadruplexes using series of ligand






















COMPUTER AIDED DESIGN OF LUFFARIELLOLIDE ANALOGUES FOR TARGETING
RETINOIC ACID RECEPTOR
Raviteja Surubhotla, Meghana Rudraraju, Tejaswi Bavineni, Suresh B Vepuri*
Institute of Pharmacy, GITAM University, Vishakhapatnam-530045, Andhra Pradesh
*For correspondence: vsb.gip@gitam.in
Cancer is a leading cause of death worldwide, accounting for 7.6 million deaths (around 13% of all deaths)
in 2008 (WHO). Deaths from cancer worldwide are projected to continue rising, with an estimated 13.1
million deaths in 2030. Majority of the drugs used today are cytotoxic, drugs that are targeted at the retinoic
acid receptor (RAR-which is a nucleoreceptor for gene suppression) were found to be more tumour
selective. Since the retinoid classes were found with more side effects, structurally similar compound
luffariellolide of marine origin which has unique binding mechanism unlike to retinoids is under
investigation. We attempted a rational drug design approach using Schrodinger Maestro software in order to
identify a lead structure binding to RAR. The RAR structure (PDB ID: 4DMQ) was taken from protein
databank. Structures similar to luffariellolide were downloaded from pubchem compound data base. Using
ligand preparation tool all the ligand structures were optimised and possible confirmations were generated.
Docking was performed using glide docking protocol of Schrodinger maestro flexible glide XP (extra
precision). Compounds with high binding affinity were selected based on dock score and the
pharmacokinetic properties were calculated using QikProp module and it was found that all the selected lead
structures had very good human oral absorption. From our study we suggest that optimisation of the
identified structures may produce better drug candidates for the treatment of cancer.

Keywords: Luffariellolide, Retionoic acid receptor, Cancer, Glide and Qikprop



























Designing of novel 7 nicotinic receptor agonists as potential therapeutic agents for the treatment of
cognitive impairments in Alzheimers disease by core hopping and molecular modeling methods
. #emya, (.). *ileep, E.+. )ariyar and . Sadasi,an-
Department of Biotechno(o,y an% Micro*io(o,y an% Inter University 'entre for Bioscience, -annur University,
Tha(assery 'ampus, &a(aya% &./., -era(a 01# 00+
- csadasi,an@gmail.com
Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of Cys-loop ligand gated pentameric ion
channels distributed in the human central nervous system. They are involved in a wide range of
physiological and pathophysiological processes and hence they have been proposed as potential therapeutic
targets for neurodegenerative and psychiatric disorders. The most abundant nAChR subtypes in the CNS are
the 42 and 7 receptors. Cholinergic hypothesis of Alzheimers disease (AD) states that memory loss and
cognitive impairments are associated with the cholinergic dysfunctions accompanied by the progressive loss
of cholinergic neurons in the brains of AD patients. The 7-nAChR is expressed at high levels in
hippocampus and cerebral cortex, the brain regions involved in learning and memory. Hence 7 subtype has
been studied extensively in recent years and evidences highlighted the need for the development of its potent
agonists, which may open new ways to treat the impaired cognitive functions. In this aspect, core hopping
has been used to design novel 7-nAChR agonists by taking nicotine as the template. Nicotinic cores were
replaced by fragments collected from different databases. Designed ligands were further filtered based on
the ADME profile. Since the extracellular ligand binding domain of 7-nAChR is structurally similar to
acetylcholine binding protein (AChBP), the structures of AChBP in agonist and antagonist bound
conformations were taken for the screening of the promising ligands. The ligands which bind preferentially
to the agonist bound conformation compared to antagonist bound conformation were selected. The human
7-nAChR structure was modeled using chimeric 7-AChBP receptor structure as the template. The selected
ligands were docked against the 7-nAChR. The pharmacophoric features and binding energies of the
designed ligands were also compared with the known 7-nAChR agonists. The details of the results will be
presented












Selective Inhibition of TNF-Alpha by Novel Heterocyclic compounds containing Thiazine Moieties
Selvam Athavan
a
, Chandrasekaran Loganathan
a
, Senthamaraikannan Kabilan
a*
a
Department of Chemistry, Annamalai University, Annamalainagar, Chidambaram, Tamilnadu-
608 002, India

Tumor necrosis factor (TNF-) is a polypeptide cytokine involved in inflammation and the acute phase
response. The overproduction of TNF- is responsible for many autoimmune disorders such as rheumatoid
arthritis, psoriasis, Crohns disease, ulcerative colitis, diabetes, multiple sclerosis, atherosclerosis, and
stroke. The discovery of clinically relevant inhibitors of TNF- has proven to be a challenging task.
To identify novel and potent inhibitors TNF-, docking studies approach became very useful and
largely widespread technique for ligand-based drug design, finally synthesis the target molecule to achieve
good activity.
We perform docking studies of some novel heterocyclic compounds containing thiazine moieties to
elucidate the structural properties required for TNF-alpha inhibitory activity. This approach showed that
hydrophobic and electrostatic effects dominantly determine binding affinities which will further useful for
the development of new lead compounds to inhibit TNF-Alpha.













In-silico study of herbal compounds with anti-cancerous activity
S. A. Harle, P. A. Wadegaonkar
Bioinformatics Infrastructure Facility (BIF), Department of Biotechnology,
Sant Gadge Baba Amravati University, Amravati 444602, Maharashtra, India.

There are several macromolecules against which the anti-cancerous drugs are targeted. The
inflammatory cytokines like NF-B, TNF, IL-1, IL-6, chemokines are among the potential targets of drugs
against cancer. In spite of several years of research through modern methodology of drug discovery, the
promising drugs are not there against the dreadful ailment. An effort is being made to study traditional
information in context with current knowledge of drug discovery and modern techniques based on those.
The advanced computational tool from Schrdinger Mastro-9.4 along with modules is used to study natural
compounds against Cancer targets.
In the present study, some of the herbal anti-cancerous compounds are docked against the cancer
targets. The compounds are taken from the literature sources and properties of these compounds are
calculated, so as to screen the dataset on the primary level in relation with modern approach of drug
discovery. The results of the molecular docking of such screened compounds provide a great insight for the
probable mechanism of anticancer leads, which are being used since time immemorial under the name of
traditional medicinal scheme like Ayurveda.
Keywords: Ayurveda, Herbal compounds, Maestro















MOLECULAR DOCKING APPROACH TO EVALUATING INHIBITORY ACTIVITY OF
CAMPTOTHECIN AND ITS DERIVATIVES ON DNA- TOPOISOMERASE I
B. Siva Kumar, Chelli Sai Manohar
Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Prashanthi Nilayam
E-mail: bsivakumar@sssihl.edu.in , chellisaimanohar@sssihl.edu.in
The pivotal role of enzyme - Topoisomerase I in multitudinous vital processes of cell cycle coupled with its
elevated level in solid tumors has rendered it a promising target for treating concerned types of cancers.
Camptothecin (CPT); the major alkaloid, extracted from the stem wood of the Chinese tree Camptotheca
acuminata, is found to be a promising drug [1, 2]. Five sets of 67 modified CPT derivatives [3, 4] were
classified depending on the position of substituents and then used for an extensive molecular docking study
upon Topoisomerase I receptor using pyrex-Autodock-Vina [5] and the binding results, pictured using
PYmol. The docking study helped arrive at linear co-relation equations between Binding-Energy and
Activity of the drug ligand for each set with appreciable linearity R
2
0.92 on an average and further a
universal co-relation equation for any CPT ligand with R
2
0.95. Deviation was largely, a result of electron
withdrawing groups in addition to minor role by electron pumping groups. Steric crowding also contributed
through non-aromatic substituents. Binding energy was enhanced by the presence of exclusive o, p directing
halide substituents - especially Chlorine. The enhancing role of electronegative groups or a net increase in
the number of electronegative substituents in the ligand was evident. Established co-relations helped predict
the unknown activity of close to 40 CPT analogues, whose IC
50
values were previously not reported, with
the best IC
50
~ 13, yet to be confirmed in vivo. Additional active Amino-acid residues for binding in the
receptor, apart from reported sites [6] were also obtained from the study.
REFERENCES
[1] Tanizawa A et al., Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of
camptothecin derivatives presently in clinical trials, J Natl Cancer Inst 1994; 86: 83642.
[2] Verweij J., Topoisomerase I inhibitors and other new cytotoxic drugs, Eur J Cancer 1995; 31: 828
30.
[3] Ai-jun, L. U. et al., 3D-QSAR study of 20 (S)-camptothecin analogs, Acta Pharmacol Sin 2007 Feb;
28(2): 307314
[4] Qingyong Li et al., Synthesis and antitumor activity of novel 10-substituted Camptothecin analogues,
Bioorganic & Medicinal Chemistry 14 (2006) 71757182
[5] O. Trott, A. J. Olson, Journal of Computational Chemistry 31 (2010) 455-461
[6] Antonino Lauria et al., Molecular docking approach on the Topoisomerase I inhibitors series included
in the NCI anti-cancer agents mechanism database, J Mol Model (2007) 13:393400
Screening of Marine Alkaloids possessing Multi-Target effect on VEGFR Pathway in Triple Negative
Breast Cancer





Saranya Sivaraj
1
, Manish Kesherwani
2
, Velmurugan Devadasan
2
, Gayathri Dasararaju
1
, *
1
Department of Biotechnology, Dr. MGR Educational and Research Institute University, Maduravoyal,
Chennai-600095, India.
2
Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy campus,
Chennai-600025, India.
E-mail: drdgayathri@gmail.com

Natural compounds are considered to be the best curative agents since ancient times and also recent works
on isolation and identification of novel natural compounds might help in treating cancer. Cellular functions
are carried out through various complex signaling pathways, which can be disturbed and might result in
cancer. In recent years, triple negative breast cancer (TNBC) is considered to be most challenging, as TNBC
basically lacks overexpression of estrogen receptor, progesterone receptor and human epidermal growth
factor-2 thereby the tumor does not respond to endocrine treatment and other targeted therapies. About 34%
of TNBC tumor is located at the chromosome 6p21.2 and 6p12 region, which includes VEGF-A. Vascular
endothelial growth factor (VEGF) helps in formation of new blood vessels so that the cell gets nourished.
Similarly when VEGF-A is activated, it binds to VEGF receptor thereby leading to the VEGF pathway
activation and that would result in activation of various other signaling processes, which promotes cell
growth, cell survival and migration. The in-silico molecular modeling and Dynamics is performed with
anti-cancer marine alkaloids to target VEGF and few of its corresponding signaling pathway enzymes such
as PI3K, Protein kinase B, MAP kinase and Cyclin dependent kinase. Virtual screening of anticancer
marine alkaloids and the existing co-crystal ligands of above chosen VEGF pathway enzymes have been
performed. Based on the glide energy and score, top seven marine alkaloids and existing 6 inhibitors were
chosen for further induced-fit docking process. Induced fit docking revealed two potent marine compounds
showing multi-target effect, which can completely arrest the progression of VEGF pathway.













On the New Inhibitors for the Resistant 5204 Strain of Penicillin Binding Protein 2B (PBP2B) of
Streptococcus pneumoniae through Structure-Based Virtual Screening
S.Suvaithenamudhan and S.Parthasarathy
Department of Bioinformatics, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024,
Tamil Nadu, India
E-mail : bdupartha@gmail.com

Penicillin-binding protein 2B (PBP2B) of Streptococcus pneumoniae leads to resistance against -
lactam antibiotics. Especially, mutations within transpeptidase (TP) domain of PBP2B of mutant strains of
S. pneumoniae lead to decreased affinity of -lactam antibiotics and thus resistance has emerged. In this
present study, the recently determined three dimensional structure 2WAE of resistant 5204 strain had been
used to perform the virtual screening analysis with 18,00,000 compounds of PubChem database through the
Virtual Screening Workflow of Schrdinger. Finally 8 compounds were selected based on glide and docking
scores. Further, Induced-Fit Docking (IFD) analysis was also performed for the above 8 compounds though
Schrdinger IFD module. The docking results show the differences in the binding affinities of these 8
compounds with PBP2B mutant of resistant 5204 strain of S. pneumoniae. Based on the glide scores, IFD
scores, binding energies and molecular interactions with active site and mutated residues, it is observed that
the PBP2B mutant resistant 5204 strain has strong binding affinity to these 8 screened compounds. The
binding patterns obtained in this present study are useful in designing potential inhibitors against Multi-Drug
Resistant (MDR) S. pneumoniae.
References
1. Pagliero E, Chesnel L, Hopkins J et al., (2004) "Biochemical characterization of Streptococcus
pneumoniae penicillin-binding protein 2b and its implication in -lactam resistance". Antimicrobial
Agents and Chemotherapy, 48:1848-1855.
2. Contreras-Martel C, Dahout-Gonzalez C, Santos Martins AD et al., (2009) "PBP active site
flexibility as the key mechanism for -lactam resistance in pneumococci". Journal of Molecular
Biology, 386:899-909.
3. Laurence M, et al., (2009) "Discovery of New Inhibitors of Resistant Streptococcus pneumoniae
Penicillin Binding Protein (PBP)2x by Structure-Based Virtual Screening". Journal of Medicinal
Chemistry, 52,5926-5936.





Androgen receptor mediated drug development to treat prostate cancer
S. Divakar
a
, K. Saravanan
b
, R. Elancheran
c
, M. Ramanathan
a
, S. Kabilan
b
, J. Kotoky
c
a
Department of Pharmacology, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India.
b
Department of Chemistry, IASST, Guwahati, Assam, India.
c
Department of Chemistry, Annamalai University, Chidambaram, Tamil Nadu, India

Adenocarcinoma of prostate gland is the 2
nd
most frequent and leading cause of cancer death in males
worldwide. Androgens particularly Dihydrotestosterone bind and activate androgen receptor (AR)
stimulating the prostate gland growth. On treatment with AR antagonist some of the PCa relapse with
incurable form of the disease namely castration resistant prostate cancer (CRPC) or androgen independent
prostate cancer (AIPC). The reasons behind the development of resistance to AR antagonist are the point
mutations expressed in AR ligand binding domain (LBD) of AIPC patients. The major mutations expressed
in AIPC patients are T877A and W741L which confer resistance to the existing AR antagonists Flutamide
and Bicalutamide respectively. The difference between wild and mutated AR is evaluated in silico using
extra precision docking mode, protein and ligand binding pocket structural alignment tools, Schrdinger.
The In silico analysis and calculation of root mean square deviation (RMSD) between wild and mutated type
ARs shows that agonist and antagonist keeps the mutated AR in active conformation. Evaluation of ligand
binding difference between wild and mutated AR using docking studies showed a major difference in the
binding mode of AR antagonist with mutated AR. From the above studies we conclude that combining
ligand and structural based drug design the new chemical entities can be developed for full antagonist that
can antagonize both wild and mutated AR.
Reference
1. Mary-Ellen Taplin, Barur Rajeshkumar, Susan Halabi, et al. Androgen receptor mutations in androgen-
independent prostate cancer: cancer and leukemia group b study 9663. J Clin Oncol.
2003;21:2673-2678.
2. Serdar Durdagi, Henry J. Duff, and Sergei Yu. Noskov. Combined receptor and ligand-based approach to
the universal pharmacophore model development for studies of drug blockade to the hERG1 pore domain. J.
Chem. Inf. Model. 2011; 51: 463474







MOLECULAR DESIGN FOR GLAUCOMA AND NON INSULIN DEPENDENT DIABETES
MELLITUS: A BETTER LEAD DESIGN BY BINDING FREE ENERGY CALCULATION

Shakthi Dasan.V & J.Jayajackison,

3RD YR, PHARMACEUTICAL TECHNOLOGY, BHARATHIDASAN INSTITUTE OF TECHNOLOGY,
ANNA UNIVERSITY, TRICHY

E-MAIL: shakthi4j@gmail.com

Ganglion cell death causes loss of vision in glaucoma by increasing the intraocular pressure due to loss of
neuroprotective strategy. Diabetes mellitus is a condition in which a person has a high blood sugar level as a
result of the body either not producing enough insulin or insulin resistance to body cells ( NIDDM ). Drug
Designing, one of the hottest topics has found its new pathway to create a history in the field of medical
science. The lead compound analysis starts with CADD, assisting to identify and optimize the right
compound. In the following study, molecular modelling method has been used for modelling a new
molecule for Glaucoma and NIDDM using Metipranolol, a drug thats already designed. Its R group is
modified by replacing different functional groups like OH, Br, CH2CH3, CH3, Cl, F, H and NH2 and
docked with specific protein with help of software. The molecules designed as such are optimized using
different
algorithms. Their affinity and binding free energy checked with protein. The molecule with minimum
binding energy will have the maximum binding affinity. From the results obtained its clear that ligand 3 and
6 ( -6.85 & -6.79 ) have the maximum binding affinity. So these molecules are determined as the best lead
molecules targeting computationally.

Keywords: Ganglion cell, Glaucoma, Diabetes mellitus, CADD, Metipranolol, Molecular modelling
technique.













Molecular Docking and Dynamic Simulation Study of luteolin as PDK-1 Kinase Inhibitor
*Shalini Singh, Rupika Sinha, Gaurav Sharma & Pradeep Srivastava

School of Biochemical Engineering, IIT (BHU), Varanasi-221005

E-Mail:*shalini.bioinfo@gmail.com

PDK-1 kinase is a master kinase, which is crucial for the activation of AKT/PKB and many other AGC
kinases including PKC, S6K, SGK. PDK-1 kinase plays a vital role in the PI3-kinase signaling pathway that
regulates gene expression, cell cycle growth and proliferation. The common human cancers include lung,
breast, blood and prostate possess over stimulation of the PDK-1 kinase signaling and making PDK-1 kinase
an interesting therapeutic target in oncology. Luteolin (plant polyphenol) inhibit the PDK-1 kinase by
binding at ATP-binding pocket revealed by molecular docking study done by Auto dock 4.0. Further,
stability of PDK-1 kinase luteolin complex is validated by molecular dynamic simulation done by
GROMAC 4.0. Luteolin was found to bind at ATP-binding site of PDK-1 with lowest binding energy-5.51
Kcal/Mol). Free energy of binding is calculated as a sum of four energy terms of intermolecular energy
(vander wall, hydrogen bond, desolvation energy and electrostatic energy), total internal energy, tensional
free energy and unbound system energy. Luteolin shows hydrogen bonding interaction with Lys111, Thr
222, Ser 160 and Ala 162. Ser 160 and Ala 162 are the hinge region amino acids which play a crucial role in
PDK-1 kinase activity.The highest scoring docking conformation of PDK-1 kinase luteolin complex
generated by Auto dock 4.0 was taken as initial conformation for MD simulation. These docking poses were
subjected for the molecular dynamics simulation for 10 ns. Number of H-bonds (cut off 0.35 nm) as well as
the RMSD profile of PDK-1 luteolin complex were also studied and found that they shows significantly
good results(RMSD < 0.5 nm). Molecular docking and dynamics simulation studies with luteolin revealed
that luteolin may act as a probable drug for treatment of cancer.
Key words: PDK-1 kinase, Luteolin, docking, simulation, Gromac, Flavanoids.







Docking and simulation of ligand molecules of Azadirachta indica against diabetes
Shraddha Jethi and Aadhya Saravgi
Department of Bioinformatics,School of BioSciences and Technology,VIT, University,Vellore,Tamil Nadu,
632014

Diabetes mellitus is a metabolic disorder of endocrine system.It is becoming a socio-economical threat in
developing countries like India. However, several attempts have been made to control and treat the disorder
using synthetic drugs. Alternatively, herbal drug screening has gone up against the diabetes. Here, we
applied computational methods to virtually screen the known active constituents of Azadirachta indica
against 1IR3 drug target. Initially we found the active site for this receptor using pocket finder and
PROSITE. Further, the active sites were docked with the ligands using Autodock and simulated by Maestro
molecular dynamics software. The PROSITE has showed that residues 1155-1167 are important for ligand
binding. The docking results suggest the hydrogen bonding interaction and their effectiveness for being a
possible antidiabetic drug.




















SELECTION OF NOVEL COUMARIN DERIVATIVES AS HDAC INHIBITORS - AN IN SILICO
PREDICTION FOR CANCER THERAPY
M. Sindhuja
1
, A. Umamaheshwari
1
, S. Gayathri
1
, A. Puratchikody
1
,

Mukesh Doble
2

1
Department of Pharmaceutical Technology, Anna University, BIT campus, Tiruchirappalli-620024, Tamil
Nadu
2
Department of Biotechnology, Indian Institute of Technology, Chennai-600036, Tamil Nadu

For a long time, cancer has been considered to be the result of a wide variety of genetic and epigenetic
alterations, such as DNA methylation and post-translational histone modifications such as acetylation,
methylation, phosphorylation, etc. Recently, our understanding of this regulatory mechanism has been
enhanced by the identification and characterization of mainly the enzyme that catalyses the reverse
deacetylation (Histone Deacetylases HDACs) whose over expression can mediate tumor cell proliferation.
Nowadays HDAC inhibitors (HDACi) are used as promising drugs for the treatment of cancer. The FDA
approved simple and synthetic pan HDACi is Suberoylanilde Hydroxamic Acid (SAHA) which is used for
the treatment of cutaneous T-cell lymphoma. The pharmacophore of SAHA is chosen for designing the
ligands in our study. Further, several synthetic coumarins with a variety of pharmacophoric groups at C-3,
C-4 and C-7 positions have shown good to moderate anticancer activity against colon, breast and lung
cancer cell lines. Hence, in the present work, one hundred and eighty five randomly selected hydroxamic
acid groups of HDACi that have dierent cap groups with coumarin nucleus were taken and several
molecular descriptors were calculated using online tools such as Molinspiration and Osiris property
explorer. Toxicity was also predicted using another online tool ADME-Tox Box. The results showed 28
compounds with relatively good drug score in comparison with SAHA and were chosen as ligands for
docking among which 6 of them showed good ADME properties. GRIP docking of SAHA and designed
ligands were carried out with the protein PDB 1T69 using Vlife Molecular Design Suite 3.5 software. The
docking analysis seems to suggest that, in addition to the predominant zinc binding group interactions, the
interactions of the capping group with the active site surface are essential. The ligands predicted to dock
well into the active site of human HDAC-8 and are considered as interesting molecules that need to
be further synthesized and tested in the laboratory.






In-silico molecular docking studies of quinazolin-4-(!"-one derivatives
*.S.$*/0+"
S2I 2AMA'3A4D2A U4IV52SIT6, 7A'U8T6 /7 &3A2MA'6, &/2U2 '3544AI 9 ++0

1uina2olin3435'/63one is a ,ersatile lead molecule 7or designing potential 8ioacti,e agents and its deri,ati,es 9ere
reported to possess 8road spectrum acti,ities. '3su8stituted3 23phenyl :uina2olin3435'/63ones 9ere reported to
contain anti3/.) acti,ity and anticancer acti,ity. ;he 7ollo9ing su8stituted compound o8eys the <.P.$S(.=S #0<E >F
F.)E.
1uina2olinones 9ere screened 7or their 9ide spectrum anti,iral acti,ity and they ha,e rich potential 7or 7urther
studies. >ur aim is to study the molecular docking studies o7 :uina2olinone 9hich is lead structure 8ind 9ith re,erse
transcriptase en2yme. #e,erse transcriptase en2yme is essential 7or ,irus con,ersion 7rom #$" to *$" ,irus.
%olecular docking studies o7 '3su8stituted 323phenyl :uina2oline 343one is done 8y using so7t9are like "uto dock
and Schrodinger 9hich gi,es ,ery good docking score 9ith re,erse transcriptase en2yme. "lkyl group su8stituted
:uina2oline gi,es targeted 8inding e77ect comparati,ely than polar su8stituted compounds. ;his paper descri8es the
/.)3? #; Function and molecular structure, illustrates the inhi8iting acti,ity o7 :uina2olinones to9ards /.)3?#;.










































Docking studies of Pyrimidine derivatives

G.Sivagamisundari, Dr.A.Mercy Pusphalatha, Julie Ranee

Department of Chemistry, Lady Doak College, Madurai


Docking studies proves to be a significant tool in predicting the binding orientation of small molecules with
the receptor protein and thus aides in the identification of innovative small molecules that possess drug like
properties. Novel Heterocyclic compounds are found to possess important biological properties. Hence the
present study was aimed at the synthesis of pyrimidine derivatives (4,6-dimethyl 2-phenylpyrimidine, 5-
acetyl 6-methyl 4-phenyl 1,2,3,4- tetrahydropyrimidin2one and their derivatives) under solvent free
microwave irradiation using Silica bonded Sulphur Sulphonic acid. The activity of the synthesized
compounds against hyperthyroidism was studied using in silico tools. Docking software Schrodinger suite
2009 was used for the docking of the designed ligand (the Synthesized pyrimidine derivatives) with the
target protein (THYROID HARMONE ) RECEPTOR. Glide 5.5 was used for ligand docking studies.
From the results obtained it was evident that the synthesized pyrimidine derivatives with the carbonyl group
in 5
th
position had stronger interactions with protein amino acid residues as there was an increase in the
glide score from -8 to -9. The substitution of Halogen and nitro group in the 4
th
position of the phenyl
moiety of pyrimidine derivatives also had higher bonding interactions with the protein. Among all the
synthesized compounds, pyrimidinone derivatives exhibited very good affinity towards the TH . Based on
the Glide score it can be concluded that the pyrimidine derivatives could be potential leads and by making
suitable modifications in the 4
th
position of the pyrimidine moieties, these can be converted to drug
molecules which possess antihyperthyroidic activity.























Explaining in-vitro xanthine oxidase activities of small molecules using eMBrAcE energies
Smriti Khanna, Chandrika B-Rao
Discovery Informatics, Piramal Enterprises Ltd., 1 Nirlon Complex, Goregaon (E), Mumbai, 400 063, India
Xanthine oxidase inhibitors are employed in the treatment of hyperuricemia which leads to gout. Main
treatments in the market for gout/ hyperuricemia are Allopurinol and Febuxostat. FYX-051 (Topiroxostat) is
currently in phase II clinical trials and has the same mechanism of action as Allopurinol. Both these
compounds co-ordinate to molybdopterin cofactor and, in the process, get hydroxylated unlike Febuxostat
which does not show metal co-ordination. Structure activity relationship of FYX-051 analogs published in
literature shows that when -CN group on FYX-051 molecule is replaced by NO
2
or COOC
2
H
5
, xanthine
oxidase inhibitory activity is retained. All these groups are capable of forming H-bonds with Asn768 in the
active site of the protein. However with COO
-
substitution, activity is lost even though it forms an H-bond
with Asn768. Similar xanthine oxidase inhibitory activity profile is observed for these substituents in our in-
house scaffold as well. Docking scores obtained using Glide XP implemented in Schrodinger Suite of
programs for FYX-051 analogs as well as our in-house inhibitors were unable to reason out inactivity of
acid derivatives compared to other substitutions. Free energy values obtained from MM-GB/SA calculations
were also not able to provide any explanation for this observation although it did give an idea that solvation
might play a role in this phenomenon. eMBrAcE (Multi-Ligand Biomolecular Association with Energetics)
minimization implemented in MacroModel module of Schrodinger was carried out to calculate association
energy of the receptor-ligand complex. It is a type of multiple minimization in which each of the specified
pre-positioned ligands is minimized, in turn, with the receptor. Energy difference mode in solvent phase
within eMBrAcE was used, in which energy changes upon association are estimated. It uses GB/SA
continuum solvation model. The energy difference E between the complex, and the ligand and the receptor
is calculated, which includes solvation effects. The E values showed good correlation with the IC50 values
of the compounds. The van der Waals and electrostatic contributions to the E values did not show any
discrimination between active and inactive compounds. However, the solvation energy component of E
values for the acid derivative was found to be distinctly high compared to other analogs. Thus, eMBrAcE
calculations explain a bigger role of solvation phenomenon for the acid derivatives in the current scenario
despite having H-bonds with the receptor active site Asn768 residue, and this could explain the difference in
their activity compared to other substituents.

References
1. Bioorg. Med. Chem. Lett. 2009, 19, 184.
2. MacroModel, version 9.9, Schrodinger, LLC, New York, NY, 2011.
















3.

Molecular Docking of VEGF receptors with phytochemicals for the applications in Tissue Engineering
Asthana S., Agarwal T., Banerjee I., Pal K., Pramanik K., Ray S.S.*

Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha
Email: *Sirsendu@nitrkl.ac.in

Tissue engineering has shown assurance for the advancement of the constructs to facilitate large volume of
soft tissue augmentation in reconstructive and cosmetic plastic surgery. This includes fabrication of
scaffolds which facilitate the growth of cells when seeded into it. But cells cannot grow without proper
distribution of nutrients. Appropriate distribution is possible only when blood vessels are there to provide
some sort of channeling throughout the scaffold. Regulated angiogenesis play a very important role in
growing the cells or tissue. Emerging evidences show that there are some phytochemicals which are
historically known to initiate wound healing and have some effect on angiogenesis. In this current study, a
computational approach has been applied to assure the role of the phytochemicals in stimulation or
inhibition of angiogenesis through modulation of Vascular Endothelial Growth Factor Receptors (VEGFR1
& VEGFR2). Molecular docking based on Lamarckian Genetic Algorithm was carried out using
AutoDock4.2 (version 1.5.6) tool. The metabolite structures were retrieved from PubChem and
KNApSAcK-3D databases. The grid maps representing the protein were calculated using auto grid and grid
size was set to 60*60*60 points with grid spacing of 0.375 . Docking was carried out with standard
docking protocol on the basis of a population size of 150 randomly placed individuals; a maximum number
of 2.5 *10
7
energy evaluations, a mutation rate of 0.02, a crossover rate of 0.80 and an elitism value of 1.
Fifteen independent docking runs were carried out for each ligand and results were clustered according to
the 1.0 rmsd criteria. Hydrogen bond analysis was done by UCSF Chimera. Molecular, ADME and
toxicity predictions were carried out using PreADMET server. Based on the docking analysis, Tuberostan
(KnapSackID_C00010049) and Puerarone (KnapSackID_C00009871) were found to have a significant
effect on the intracellular domain of VEGFR1 and VEGFR2 with a binding energy of -9.32 and -9.19
respectively. Both the molecules exhibited good drug-likeness model score, encompassed good ADME
properties and showed no carcinogenic and toxic effects. Further in-vitro and in-vivo study is required for
the future design of new derivatives with higher potency and specificity.

(ey9ords: "ngiogenesis, )E@F#?, )E@F#2, ;u8erostan, Puerarone, %olecular *ocking, "*%E A ;ox.





















Role of Vitamin C as a Collagenase Inhibitor (Human MMP)
Dr.B.Sreedhar, Dr.T.V.Rao, Sree Lekha Revur, Sai Shashank Chavali
Department of Biotechnology, KL University, Guntur, AP
It is well established that the over expression of MMP is the key event in several pathological and
physiological conditions. Collagenases, including MMP-1,-8,-13 are collagen degrading enzymes, belonging
to the MMP family, which are involved in diseases like rheumatoid arthritis and osteoarthritis. It has
remained a challenge over the years to find a potential inhibitor that can successfully meet clinical trials, for
this problem. On the other hand, there is ample evidence supporting Vitamin-Cs role in Collagen
biosynthesis. Recent studies, threw light on expression of MMP-1, at mRNA level can be regulated by
Vitamin C. We hypothesized that Vitamin C may also have an inhibitory action on MMP-1, which turned
out to be positive in Molecular Docking Studies, (Schrodinger).The hydroxyl moiety of Vitamin C is found
to be interacting with the active Zinc component of MMP-1. Like any other potential inhibitor of MMPs,
catalytic site exhibited three Histidines (His-118,-122,-128) ,to be coordinating the active site of Zinc,
Hydrolysis of peptide assisted by Glu-119, and loss of a Proton molecule. All these evidences make it more
convincing to believe that Vitamin C may serve the purpose of potential MMP inhibitor.

































In silico docking analysis of neuroprotective and cytoprotective activity of phytoconstituents
identified in selected medicinal plants
Srikanth.J
1*
, Kavimani. S
2
, Uma Maheswara Reddy C
1
, Chitra. K
3

1
Department of Pharmacology, Faculty of Pharmacy, Sri Ramachandra University, Porur, Chennai 600
116, Tamil Nadu, India
2
Dept of Pharmacology, Mother Theresa Post Graduate and Research Institute of Health Sciences,
Puducherry - 605006, India
3
Department of Pharmaceutical chemistry, Faculty of Pharmacy, Sri Ramachandra University, Porur,
Chennai 600 116, Tamil Nadu, India

Email ID- srikanthcologist@gmail.com, Mobile- 09094020093
Introduction: In the field of drug discovery, reverse pharmacology also known as target base drug
discovery (TDD), a hypothesis is first made that modulation of the activity of a specific protein target will
have beneficial therapeutic effects. Screening of chemical libraries of small molecules and phytoconstituents
identified in plants is then used to identify compounds that bind with high affinity to the target. The hits
from these screens are then used as starting points for drug discovery. This method became popular after the
sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified
proteins.
Aim & Objective: The aim and objective of the present study is to carry out a reverse pharmacological
evaluation by performing in silico docking analysis of the active constituents identified in three medicinal
plants namely Bacopa monnieri, Withania somnifera and Morinda citrifolia for neuroprotective and
cytoprotective activity.
Materials & Methods: In silico docking analysis was performed by using Molegro Virtual Docker. The
parameters used for the docking analysis are MolDock score; Rerank score and HBond interactions (Binding
energy). The targets for neuroprotective activity are identified as acetylcholine esterase, butyryl choline
esterase and for cytoprotective activity as thymidylate synthase & P-Glycoprotein. The X-ray crystal co-
ordinates of acetylcholine esterase (PDB ID: 1B41), butyryl choline esterase (PDB ID: 2PM8) thymidylate
synthase (PDB ID: 1HVY) and P-Glycoprotein (PDB ID: 3G61) were retrieved from protein data bank in
.pdb format. The phytoconstituents of the three medicinal plants were retrieved from pubChem compound
database in .mol format.
Results & Discussions: The comparative neuroprotective and cytoprotective activity of the
phytoconstituents of three medicinal plants are analysed by docking score and binding energy. It was
analysed from the parameters of docking that the phytoconstituents from Morinda citrifolia showed better
cytoprotective activity and that the phytoconstituents from Bacopa monnieri showed better neuroprotective
activity. Further studies can be carried out to test the drug like properties of the phytoconstituents
according to the Lipinski rule of 5 and to develop them as potential lead compounds for neuroprotective
and cytoprotective activity.
Key words: Medicinal plants, Docking, Neuroprotective, Cytoprotective.






STRUCTURE-BASED VIRTUAL SCREENING APPROACH TO THE DISCOVERY OF SMALL
MOLECULE INHIBITORS OF HIF- PROLYL HYDROXYLASE
D ANANTHAKRISHNAN, Dr.Suganakala
A V C College Mayiladuthurai
Hypoxia plays a crucial role in the pathophysiology of acute kidney injury (AKI) and presumably also
chronic kidney disease (CKD). Under hypoxic condition Hypoxia-inducible factor (HIF) is most active
which helps the kidney cells to produces EPO, the primary peptide hormone that directly stimulates the
process erythropoises to maintain normal hemoglobin. Under normoxic condition HIF is quickly
hydroxylated via a Hypoxia inducible factor prolyl hydroxylase (HIF-PH) and subsequently degraded via
the proteasome pathway. The inhibitors of factor-inhibiting HIF-1 (FIH1) have been shown to be useful as
therapeutics for the treatment of anemia. In this study, we identified binding sites for HIF PH domain and
demonstrated the successful use of structure-based high throughput virtual screening to identify inhibitors of
HIF Prolyl hydroxylase. Further, we analyzed the ADMET Properties for the novel compound and this
will provide an impetus for the development of better inhibitors and ultimately lead to the discovery of the
first oral therapy for the treatment of anemia in CKD.














In silico activity profiling of flavonoids and isoflavonoids in substrate competitive inhibition of
SULT1A1 in breast cancer
Sugunakar Vuree
1
, Altaf Ali
1
, Aravind Setti
1
, MukeshYadav2, Anuraj Nayarisseri
2
, Pratibha Nallari
1
and
S.Vishnupriya
1
1. Department of Genetics, Osmania University, Hyderabad- 500007.
2. Department of Pharmaceutical Chemistry, Soft vision College, Indore-452010.
Email: sugunakarvure@gmail.com
SULTs play an important role in the homeostasis of the body in two ways. First: by sulfoconjugating drugs
and xenobiotic compounds for their removal via hepatobilliary and urinary systems; second, by
sulfoconjugating and deactivating endogenous active substances. In mammalian species, SULTs are found
throughout the body in the gut, liver, kidneys, adrenal and thyroid glands, lungs, reproductive organs, breast
tissue, brain, and blood. More than 65 distinct SULT enzymes, spanning 33 isoforms, have been identified
and characterized, 11 of which are human sulfotransferases (hSULTs).
Isoflavonoids and flavonoids may interact with estrogen receptors, but they also have a diverse range of
other biological effects including antiviral and antioxidant properties, interactions with enzymes and
pathways associated with control of the cell cycle, and effects on xenobiosis. We have previously suggested
that these compounds may also disrupt the metabolism of endogenous estrogens. Intracellular concentrations
of flavonoids have not been reported in the literature, but if they reflect those found in the plasma and if
these compounds are able to interact with sulfotransferases as we have observed in vitro, the activity of
SULT1A1 would be greatly reduced by their presence. Moreover, by acting as substrates for SULT1A3 and
other cytosolic sulfotransferases, high concentrations of flavonoids might rapidly exhaust the available
supplies of PAPS, thereby effectively inhibiting all sulfotransferase activity.

The reports suggest that large doses of dietary isoflavonoids may have a profound effect upon the
metabolism of steroid hormones in humans, possibly leading to elevated levels of active estrogens in target
tissues including mammary gland. These changes are unlikely to offer any protection against breast cancer
and could be deleterious for those in the early stages of the disease or at particular risk of developing it.
Hence, there are good reasons to question whether the widespread use of these compounds in dietary
supplements is wise, and there is an urgent need for further work to clarify this issue.

To above concern, we decided to investigate structure based profile of flavonoids and isoflavonoids using
exhaustive computational techniques. We offered molecular modeling, mutagenesis in SULT1A1, molecular
docking and pharmacokinetic and pharmacodynamics studies in silico. The results confirm considerable
activity between SULT1A1 and flavonoids and isoflavonoids derivatives as competitive inhibitors, though,
activity of various derivatives differ to wild and mutated isoforms of SULT1A1.

Key words: Sult gene, Isoflavonoids, flavonoids and Docking etc.







Rational Drug Design For Identifying Novel Target Inhibitors for Tuberculosis with Components of
Asparagus racemosus
Pallavi Dutta,Supriya Chakraborty,Bijita Banik,Sudip Ghosh, Abhinav Roy, Annesha Chakraborty ,Subrata
Sinha, Surabhi Johari*
Center for Bioinformatics Studies, Dibrugarh University, Dibrugarh,India
E-mail:surabhibiotech1@dibru.ac.in
Pulmonary Tuberculosis (TB) is known as a contagious bacterial infection caused by Mycobacterium
tuberculosis (M. tuberculosis), that involves the lungs and gradually effects to other organs. It has been
discovered that MTB interfere with cellular transduction pathway that are activated by Interferon-gamma or
IFN-and also inhibits IFN- . Thus inhibition of IFN- induced CIITA(Class II Transactivator) by MTB
19-KDa lipoprotein and allows MTB to evade detection by CD4
+
T-cells. So its activation plays a very
important role. Asparagus racemosus is a medicinal plant which has been used from early days as ayurvedic
medicines. In this paper an attempt has been made to establish components activities in-silico with IFN-
that is responsible for activation of macrophages. We found that among the seven screened components,
Pseudoprotodioscin interacts potentially with IFN- with satisfied drug-score and drug-likeliness. It is
highly soluble, highly permeable, non-mutagenic, non-tumorigenic and non-irritant.

Keywords Pulmonary Tuberculosis, Mycobacterium Tuberculosis, IFN-, CIITA, 19-KDa lipoprotein,
CD4+ T-cells, Pseudoprotodioscin













Molecular docking of Lupeol with Cyclin dependent kinases as potential anticancer drug target
Swati N. Hade, P.A. Wadegaonkar

Bioinformatics Infrastructure Facility (BIF), Department of Biotechnology, Sant Gadge Baba Amravati
University, Amravati 444602, Maharashtra, India

A number of natural compounds have been reported to possess anticancer properties. Their mechanisms of
action are not well understood. Lupeol a natural triterpenoid,which has been shown to exhibit various
pharmacological activities under in vitro and in vivo conditions. It is one of the potentially efficacious
dietary phytochemical that could be used in the prevention and treatment of cancers.

Preliminarily to investigate the potential molecular targets and to conrm the experimental activity
testing for the anticancer compound, the docking was performed using cyclin-dependent protein kinase
which is involved in cell cycle, cell growth, and DNA replication. Cyclin dependent kinases (CDKs) are
known as cell cycle regulators in eukaryotic cell cycle. However, tumour-associated cell cycle defects are
often mediated by alterations in cyclin-dependent kinase (CDK) activity.

In the present work different CDKs (CDK2, CDK4 etc.) were docked against naturally occurring
terpene based compound lupeol using Maestro 9.4 modules. Primary screening on the basis of molecular
properties, Lipinskis filters and ADMET was evaluated using Maestro modules to come up a lupeol as a
potential anticancerous agent.

Keywords: Lupeol, CDKs, Maestro


















Insilico Discovery of Lead Structures to treat Migraine
Tejaswi Bavineni, Meghana Rudraraju, Raviteja Surubhotla, Suresh B Vepuri*
Institute of Pharmacy, GITAM University, Visakhapatnam-530045, Andhra Pradesh
E-mail: vsb.gip@gitam.in
Migraine is the most common neurological condition in the developed world. Migraine is a condition
characterised by one sided headache that may be linked with other symptoms. It affects many people all over
the world yet it is most neglected and least funded when compared to its impact. In initial stages analgesics
are prescribed for pain management. Presently a class of drugs called triptans is in use which shows
agonistic activity on 5HT1B receptors (vasoconstriction). But they have many adverse effects one of which
is the recurrence of migraine. Therefore a new class of drugs is in need. We attempted a rational drug design
approach using Schrodinger Maestro software in order to identify a lead structure for binding to 5HT1B.
The 5HT1B receptor (PDB ID: 4IAR) is taken from protein data bank. As the target being 5HT1B receptor
compounds similar to serotonin neurotransmitter (1068 compounds) were taken from PubChem compound
database. Using ligand preparation tool all the ligand structures were optimized and possible conformations
(8083 compounds) were generated.
Docking was performed using glide docking protocol of Schrodinger maestro flexible glide XP (Extra
precision). Compounds with high binding affinity were selected based on the dock score and the
pharmacokinetic properties were calculated using quick prop module and it was found that 40% of the
selected lead structures had more than 75% human oral absorption. From our study we suggest that
optimization of the identified structures may produce better drug candidates for the treatment of 5HT
1
B
associated disorders like migraine.
Keywords: Seretonin, 5HT1B, Migraine, Glide and Qikprop














Insilico modification of Some Novel Tetrahydroquinoline Analogs as Potential Non-Nucleoside
Reverse Transcriptase Inhibitors

*TINKU MONDAL, Dr. VINEETH CHANDY,
1
SWAGATAT DUTTA ROY,

* Post Graduate Department of Pharmachemistry: T.John College of Pharmacy, Gottigere post, Banglore-
560042, Karnataka,
1
Post Graduate Department of Pharmaceutics: Smt. Sarojini Ramulamma College of Pharmacy.

E-mail id: bhromor.kolkata@gmail.com, Tel: 9591190807,

Abstract:
In our present study, we tried to develop a tetrahydroquinoline based non-nucleoside reverse
transcriptase inhibitor by means of an in-silico drug design study for lowering the burden of the synthesis. A
series of 14 molecules were designed considering the tetrahydroquinoline nucleus as a core moiety. The
least energy conformers were generated and docked virtually using AUTODOCK 1.4.6 with the target,
reverse transcriptase enzyme. Prior docking operation, the enzyme was fed into CHIMERA software and
Ramachandran plot, thereby; the extent of favorable and unfavorable zone of the enzyme was identified.
Most of the molecules have shown a significant docking interaction with promising docking score.
Compound 1(a) was found to achieve the highest binding energy: of -7.14 Kcal/mole, thus placed itself quite
conveniently with the receptor active binding pocket. With the rest of the molecule in the aforementioned
series, the binding energy lies within the range of -4.89 to -6.86, which was also very significant in context
to effective drug receptor interaction. Most of the compounds have shown a butterfly like orientation around
the active binding site. The surrounding residue alignment of the designed molecule shows the exact residue
alignment as per need of the NNBS pocket. Hence, the present work enforce us to optimize those suitable
compounds by means of synthesis, if further optimized through biological evaluation may prove to be as
effective as novel selective and potent Non- Nucleoside Reverse Transcriptase inhibitors for the treatment of
AIDS.









Assessment of Molecular Binding of Hoechst 33258 Analogues into DNA Using Docking and
MM/GBSA Approach
Upasana Issar, Tripti Kumari & Rita Kakkar*
Computational Chemistry Laboratory, Department of Chemistry,
University of Delhi, Delhi-110007, India

E3mail: rkakkar@chemistry.du.ac.in
In order to understand every aspect of interaction between minor groove binders based on Hoechst 33258
and the double helical B-DNA dodecamer, a molecular modeling study has been performed on Hoechst
analogue-DNA complexes. Using combinatorial design with structural modifications, a diverse ligand
library of two hundred and fifty analogues of Hoechst 33258 has been prepared. Molecular interactions and
binding affinities of these analogues, differing in their central cores, with nucleic acids are studied using
molecular docking and MM-GB/SA methods. Results show that the presence of hydrogen bond donors,
aliphatic piperazinyl ring and rotatable bonds is the essential requirement for optimal DNA binding of
Hoechst analogues. Mainly, the bisubstituted and trisubstituted phenyl analogues, rich in hydrogen bond
donors, display good recognition towards AATT rich DNA sequences, affirming all reported experimental
observations. The analogues that have benzoxazole, benzothiazole and pyridine substituted benzimidazole
show preference towards GGCC rich DNA rather than CCGG, AATT and TTAA rich DNA. From the
induced fit docking analysis, we have found that the binding site of these analogues consists mainly of
GCCA or TGGC sequences. Here, the guanine base acts as both a hydrogen bond donor and hydrogen bond
acceptor for this heteroatom substituted analogues, thereby holding them with greater ease. In all, our work
satisfactorily explains the variation in drug-DNA recognition on altering the basic nature of Hoechst.
















Docking Studies on Phytoconstituents of Moringa Olifera as DNA Gyrase Inhibitors
Valentina.P*, Ilango.K, Anita Priyadharshini.K and Kiruthiga.B
Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM University, Kattankulathur-
603203
The plant kingdom represents a rich storehouse of organic compounds, many of which have been
used for medicinal purpose and could serve as lead for the development of new drugs. A plant
with high medicinal value is Moringa olifera belonging to the family Moringaceae , commonly
known as Drumstick in English. It is a tree cultivated throughout India for different purposes such
as medicine, vegetable, spice and cosmetic oil. Traditionally, this plant is used as antispasmodic,
stimulant, expectorant and diuretics. The bark of the plant is reported to have antifungal and
antibacterial activities. The plant also possesses cardiac circulatory and antiseptic properties. In traditional
medicine, the leaves are believed to affect blood pressure and glucose levels and given for nursing mother in
belief they increase lactation. From the review of literature, the whole plant is found to have nearly
about 25 phytoconstituents. The present work is to evaluate the antibacterial activity of this plant by
Molecular docking. DNA gyrase is a type II Topoisomerase is the target for many antibiotics like
Nalidixic acid, Novobiocin and Ciprofloxacin. Very recently, gyrase has been found in malarial parasite
Plasmodium falciparum. Based on the above facts, the current work is planned to explore the DNA
gyrase inhibitory activity on the reported phytoconstituents present in Moringa olifera by means of
molecular docking, thus acting as a template for the complete evaluation of the various medicinal properties
reported for the plant
















Modulating effect of Embelin and its ninhydrin adducts against PPAR- & HMG-CoA: In silico and
In vivo studies

Veerapur VP
1
*, Thippeswamy BS
2
, Shankar G. Alegaon
3

1
Department of Quality Assurance
2
Department of Pharmacology, Sree Siddaganga College of Pharmacy, BH road, Tumkur-572102,
Karnataka, India
3
Department of Pharmaceutical Chemistry, KLE Universitys College of Pharmacy, Nehrunagar, Belgaum-
590 010, Karnataka, India
E-mail: veeresh36@gmail.com

A serendipitous observation while identifying one of the plant constituents using ninhydrin as chromogenic
reagent resulted in a nihydrine adduct with potential free radical scavenging, anti-inflammatory and anti-
diabetic properties. Based on these promising results, in the present study we are reporting in silico studies
using Schrodinger software and in vivo animal studies. The docking of computationally designed Embelin-
ninhydrin analogs with PPAR- (2XKW) and HMG-CoA (1T02) revealed varied degree of binding abilities.
Embelin (EMB) and its ninhydrin adduct (ENA) showed better activity and followed Lipinskis rule of five.
Docking score of EMB & ENA to PPAR- was found be -7.3 & -7.663 and to HMG-CoA was found to be -
3.792 & -3.27 respectively. Based on docking and application of lipinsks rule, EMB and ENA were
subjected to in vivo studies.
Antihyperlipidaemic activity of EMB & ENA in oral fat tolerance test and fructose-induced
hypertriglyceridaemia in mice was carried out. Treatment of EMB (25, 50 mg/kg, p.o) showed good
tolerance to exogenously administration of olive oil. Whereas, administration of ENA (25, 50 mg/kg, p.o)
did not reduced the triglycerides over the period of 4 h and also failed to improve the oil tolerance. This
suggested that, only EMB is able to inhibit the enzyme lipase but not ENA. Administration of both EMB
and ENA exhibited significant altered (P<0.5; P<0.01; P<0.001) in fructose-induced hypertriglyceridaemia.
ENA exhibited higher protection against fructose-induced hypertriglyceridaemia than EMB probably due to
the higher interaction (docking score) with PPAR-. The present study demonstrated new property of
embelin (EMB) and its ninhydrin adduct (ENA) as a potent lipid lowering agent and it may contribute to its
antidiabetic, cardioprotective and anti-atherosclerotic role.
Key words: Embelin, ninhydrine adduct, Lipid lowering, Docking, Lipinskis rule












MRCD an aboriginal technique in identification of nearest native conformation and design of new
antifolates towards ABL kinase

L. Yamini, B. Saikrishna, Mustafa Kamel, and M. Vijjulatha
*
Molecular Modeling and Medicinal Chemistry Group, Dept. of Chemistry, Nizam College, Osmania
University, Hyderanad- 500001
E-mail:ylingala@gmail.com and vijjulathamanga@gmail.com

In the process of designing new antifolates towards Chronic Myelogenous Leukemia (CML) multiple
receptor conformation docking (MRCD)
1
a new and indigenous technique was applied on ABL kinase.
CML is a hematopoietic stem cell disorder caused by the fusion gene called BCR-ABL. The fusion gene
encodes a protein with deregulated tyrosine kinase activity, and play a central role in the initial development
of CML. Imatinib is the only drug functions through competitive inhibition at the ATP-binding site of
tyrosine kinase domain in bcr-abl protein and prevents bcr-abl from phosphorylating tyrosine residues of
substrate proteins. Thus, by occupying and blocking the ATP binding site, it stops the signal transduction
pathways that lead to leukaemic transformation. Despite the outstanding results obtained so far,
development of resistance against imatinib with re-activation of BCR-ABL kinase activity is a major
problem in Imatinib treated patients. Hence, it opened an area of research to design new potent molecules
towards resistant strains of ABL kinase. In order to accomplish this task, new technique of MRCD
developed using Schrodinger Glide4.2
2
was applied successfully on the set of 47 molecules as ABL kinase
inhibitors
3
. Molecules were docked into 14 different conformations of the protein to identify the nearest
native conformations in the meristate binding pocket of ABL kinase. These conformations were further
subjected to CoMSIA analysis to develop superimposition independent 3D QSAR equation to approve and
quantify the technique implemented. This has shown interesting results with the quantification parameters
like q
2
, R
2
and R
2
pred
values as 0.544, 0.974 and 0.543 respectively for the training set and test set
molecules. To identify the structural requirements for designing new molecules contour maps were
generated. These structural requirements are helpful in designing new inhibitors towards Imatinib resistant
ABL kinase. This indigenous technique of MRCD in combination with other techniques can be applied
successfully to optimize the results and rationalize the process of structure based drug design techniques
towards biologically active drug targets.

Core structures of molecules taken for the study
Ref:
1. Sreekanth. S and Vijjulatha. M., J. Mol. Model., 2012, 18, 569-582.
2. Schrdinger, LLC, New York, NY, Glide, Version 4.2, 2010.
3. Sim T., Gray. N. S., and et al., J. Med. Chem., 2010, 53, 69346946













IDENTIFICATION OF SYNTHESISED ANALOGUES OF SPIROXINDOLE, PYRAZOLE AND
PYRROLE AS POTENTIAL THYMIDYLATE SYNTHASE AND P-GLYCOPROTEIN
INHIBITORS FOR ANTI-CANCER ACTIVITY BY IN-SILICO DOCKING STUDIES
C.Vinodhini*
1
, J.Srikanth
2
, Paramasivan.T.Perumal
3
, K.Chitra
4

1.Presenting author, Assistant Professor, Department of Pharmaceutical Chemistry ,Faculty of Pharmacy,
Sri Ramachandra University,Porur,Chennai-116.Tamilnadu,India.
2. Lecturer, Department of Pharmacology, Faculty of Pharmacy, Sri Ramachandra University, Porur,
Chennai-116, Tamilnadu, India.
3. Emeritus Scientist, Organic chemistry department, Central Leather Research Institute (CLRI), Adyar,
Chennai-20
4. Vice-Principal, HOD, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sri Ramachandra
University,Porur,Chennai-116.

Problem statement: In recent years design and synthesis of pharmacologically relevant heterocyclic
molecules by combinatorial technique have proven to be promising strategy in the search for new
pharmaceutical lead structures. Heterocyclic systems with a spiroxindole , pyrazole and pyrrole nucleus
represent the most spectacular example of privileged molecule in medicinal chemistry as their derivatives
have been shown to display a wide spectrum of biological activities such as anti-inflammatory, anti-viral,
cytotoxic, anti-fungal etc. The search can be focused on potential analogues of these heterocyclics that may
offer treatment for cancer as these derivatives form the basis of a large number of pharmacological products
with anti-cancer activity.
Objectives: Based on all the relevant findings, this work aims to design and synthesis a new series of
30 compounds structurally containing spiroxindole (SV), pyrazole (PV), pyrrole (VAZN) ring with better
yield, shorter reaction time and characterized by spectral studies. As an attempt to identify the potent lead
they were subjected to flexible docking study against thymidylate synthase (PDB ID:1HVY) and P-
Glycoprotein (PDB ID:3G61) retrieved from protein data bank using Molegro virtual docker (MVD).
Results: Among the compounds analysed 15 compounds namely
SV1,SV5,SV6,SV7,SV8,PV2,PV4,PV7,PV8,PV10,VAZN1,VAZN4,VAZN6,VAZN9,VAZN10 have
shown good affinity towards both the targets with significant docking score range(-87.45- to -122.80)
compared with the Raltitrexed (-116.85) and Vincristine (-82.56).
Conclusion: Furthermore, the in-vitro anti-oxidant results were used to better define of lead
compounds as good anti-oxidants, supported the docking results. Efforts are currently being taken up to
optimize the lead compound and the results of which will be the basis of future in-vitro and in-vivo anti-


cancer studies in MCF-7 and HT-29 cell lines.





DOCKING STUDIES OF NOVEL HETEROCYCLES DERIVED FROM BIS 1, 2, 4 TRIAZOLES
AGAINST HUMAN DNA TOPOISOMERASE
B. Vishwanathan*, B.M Gurupadayya, Stephen Philip.
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysore
Type II topoisomerases resolve the topological problems of DNA by transiently cleaving both strands of a
DNA duplex to form a cleavage complex through which another DNA segment can be transported. Drugs
such as etoposide, increases the steady- state level of cleavage complex, leading to DNA breakage and death
of cancer cells. Many dimeric compounds designed as bis-DNA intercalators have been evaluated as
possible anti-cancer agents. Considering the need for newer dimeric bis-DNA intercalators, efforts have
been made to screen virtually a new series of bis-triazoles derivatives by incorporating various modifications
using groups such as diethyl carbamoyl,thioester, hydrazide, oxadiazole and pyrazole. Later the drugs were
subjected to molecular docking studies using SYBYL X 2.0. The docking studies were performed on DNA
topoisomerase II using etoposide as ligand. The protein was subjected to minimization and protomol
generation using the standard protocol. The designed compounds were docked in the active site and docking
scores revealed that the compounds possess high affinity towards intercalation of DNA topoisomerase.
Among the compounds, 5C generated a good docking core (11.5313) and showed interactions with,
glutamine 778 HE22, glutamine 778HE21, lysine 456 and aspartic acid 479 at a distance of 2.364 A, 2.253
A, 2.230A and 2.567A respectively.
Keywords: SYBYL X 2.0, Docking, DNA topoisomerase , Triazole.











Insilico Studies of Natural LEAD Structures Targeting Influenza
H. Jemmy Christy, Prashant Saxena
Department of Bioinformatics, Sathyabama University, Chennai-600119
Email:prashant347@gmail.com
Influenza spreads around the world in seasonal epidemics, resulting in about three to five million yearly
cases of severe illness and about 250,000 to 500,000 yearly deaths, rising to millions in some pandemic
years. In the 20th century three influenza pandemics occurred, each caused by the appearance of a new
strain of the virus in humans, and killed tens of millions of people. Often, new influenza strains
appear when an existing flu virus spreads to humans from another animal species, or when an existing
human strain picks up new genes from a virus that usually infects birds or pigs. An avian strain named
H5N1 raised the concern of a new influenza pandemic after it emerged in Asia in the 1990s, but it
has not evolved to a form that spreads easily between people. Neuraminidase is the major drug target for
controlling disease progression. Nueraminidase plays a crucial role in the further release of influenza virus
from infected cells and spread of thi s virus within the host. In our study, we have subjected naturally
occurring compounds in plants to comparative docking studies with two approved drugs namely Oseltamivir
and Zanamivir. Previous studies have shown that the selected compounds are natural inhibitors of
Nueraminidase. The idea of this research is to find or toidentify inhibitors from the selected
compounds with better binding efficiency with the target as compared to existing drugs.
Keywords: Influenza, Neuraminidase, Zanamivir, Schrodinger-Glide.
















STRUCTURE BASED DRUG DESIGN OF HYDROXAMIC ACID, N-HYDROXY-N'-
AMINOGUANIDINE DERIVATIVES AS HDAC8 INHIBITORS AND ITS DOCKING STUDIES
USING MOLECULAR MODELLING TOOL
Avisek Mukhopadhyay*, Swastik Majumdar, Subhankar Das, Avik Roychowdhury
Birla institute of technology, Mesra, Ranchi, Jharkhand-835215, India (Department of pharmaceutical
chemistry)
The balance of histone acetylation and deacetylation which plays a critical role in the regulation of gene
expression. Histone acetylation induced by histone acetyl transferases (HATs) is associated with gene
transcription, while histone hypoacetylation induced by histone deacetylase (HDAC) activity is associated
with gene silencing. Altered expression and mutations of genes encoding HDACs have been linked to tumor
development since they both induce cell proliferation, cell-cycle regulation and apoptosis. HDACi have
become promising anticancer agents in recent years. They have shown ability to block angiogenesis and cell
cycling, as well as initiate differentiation and apoptosis. HDAC8 (HDAC subtype) inhibition has recently
been clinically validated as a new therapeutic strategy for cancer treatment with the FDA approval of
suberoyl anilide hydroxamic acid (SAHA) for the treatment of cutaneous T cell lymphoma. A novel series
of hydroxamic acid, N-hydroxy-N'-aminoguanidine derivatives were designed virtually considering the
basic pharmacophore of suberoyl anilide hydroxamic acid. The least energy conformers of each molecule
was generated and docked with human histone deacetylase (PDB id: 1T69) using molecular modeling tool
(AUTODOCK 4.2). The standard molecule SAHA has shown a free binding energy of -7.04 kcal/ mol and
the virtually designed ligand molecules are found to be similar to that of SAHA. The RMSD values of the
molecules are found to be within 2.5. By analyzing the binding mode we can report that these molecules
are promising ones for HDAC8 inhibition.
Keywords: HDACi, Hydroxamic acid, N-hydroxy-N'-aminoguanidine, Docking(AUTODOCK4.2)















Structural analysis and lead interaction studies of G72, for schizophrenia gene

Shambhu MG
1
,Manjunath BK ,Tanusree bhattacharya, Megashree, Ovya, Priyanka

The Oxford College of Engineering Bangalore, India-560068

Schizophrenia is a neurodegenerative disorder that occurs worldwide and can be difficult to diagnose. It is
the foremost neurological disorder leading to suicide among patients in both developed and underdeveloped
countries. D-amino acid oxidase activator (DAOA), also known as G72, is directly implicated in the
glutamateric hypothesis of schizophrenia. It activates D-amino acid oxidase, which oxidizes D-serine,
leading to modulation of the N-methyl-D-aspartate receptor. Thesre is need to find prefect template for
DAOA and Using GLIDE software we need to study protein ligand docking and The predicted interactions
might serve to inhibit the disease-related allele. It is assumed that current bioinformatics methods will
contribute significantly to identifying, analyzing and curing schizophrenia. There is an urgent need to
develop effective drugs for schizophrenia, and tools for examining candidate genes more accurately and
efficiently are required.

Keywords: Schizophrenia, Bioinformatics, Modeling, Docking, DAOA



















In Silico design of drugs for venous thromboembolism and related cardiovascular
diseases
Abhay Krishna and Arpita Yadav*
Department of Chemistry, University Institute of Engineering and Technology, CSJM University, Kanpur
208024 (U.P)
E-mail: abhaykrishna51@gmail.com, arpitayadav@yahoo.co.in

Thromboxane A
2
(TxA
2
) plays a major role in platelet aggregation and smooth muscle contraction.
Inhibition of TxS can be utilized for designing anti-inflammatory drugs and drugs for venous
thromboembolism. Thromboxane receptor (TPR) antagonists and thromboxane A synthase (TxAS)
inhibitors have not been clinically successful so far. The acceptance of a variety of substrates by TPR adds
to the problems apart from pharmacokinetic issues. TxS inhibition can lead to a build up of PGH
2
that can
activate TPR as well. Utilizing synergistic effect of TxS inhibition and TPR antagonism is therefore a better
option. This study utilizes molecular modeling and docking to explain drug-receptor interactions at
thromboxane synthase active site and also interactions of antagonists with TPR binding site. Role of heme
in TxS inhibitor is also highlighted. An attempt has been made at utilizing natural lead compound
bromelaine for designing dual TxS/TPR inhibitor to benefit from their synergistic effect.
References
1. L.H.Wang and R.J.Knlmacz, Prostaglandins & other Lipid Mediators. 68-69, 409-422, 2002.
2. V. Vllrich and R. Brugger, Angew Chem. Int., Ed. Engl. 33, 1911-1919, 1994.
3. M. Abramovitz, M. Adam, Y.Boie et al, Biochem. Biophys. Acta. 1483; 285-293, 2000.
4. A. Krishna and A. Yadav, J. Mol. Modeling, Vol.18(9), 4397-4408, 2012.














Modeling and Docking Studies on Dopamine D2 receptor protein to identify potent ligands for the
treatment of Parkinsons disease
B. "kshay
B
, %. Sathish
#$
, P. "khil
-%
, ( Shi,kumar
%

#Disc faci(ity, 2a)iv Gan%hi center for Biotechno(o,y, Trivan%rum, -era(a, In%ia
E3mail:akshay8hatnagar2C&0@gmail.com
Parkinson's disease (PD) is a neurodegenerative disorder of the central nervous system [1]. The main
cause of Parkinsonism is inappropriate and ineffective binding of dopamine neurotransmitter to the
Dopamine d2 receptor, which causes the loss of signal transmission through neurons [2]. Due to the
availability of neurotoxins that selectively target monoaminergic (in particular, dopaminergic) neurons [3], it
becomes important to find alternatives for dopamine.
Here I present a computational approach to depict the initial steps for the discovery of a ligand that can
effectively bind to the receptor protein Dopamine d2. In this study, the d2 receptor protein was modeled
using d3 receptor protein (Pdb id 3PBL) as template using modeler software. Then the modeled protein was
docked against various drugs (DrugBank) and chemicals (PubChem) using Schrdinger Docking Package
for protein-ligand docking.
The results showed that Plerixafor and Dopexamine with docking score -9.14 and -7.93 respectively can
efficiently bind to the receptor protein and can mimic the function of dopamine. It is interesting to observe
that Levodopa which is used as a drug for treatment for Parkinsons disease [4] is having the dock score of -
5.88 against the same modeled protein. Plerixafor and Dopexamine have also qualified the Absorption
Distribution Metabolism Elimination and Toxicity test (ADMET) which proves them as a potent candidate
to become a drug for the treatment of Parkinsons disease.
Keywords: Parkinsons disease, Dopamine, Docking, Plerixafor, Dopexamine, Levodopa, ADMET.
References:
1) Grabli D. [Parkinson's disease: new explanatory concepts focused on the cellular mechanisms]. Rev Prat.
2013 May; 63(5):634-8. Review. French. PubMed PMID: 23789487.
2) Wei W, Li L, Yu G, Ding S, Li C, Zhou FM. Supersensitive presynaptic dopamine D2 receptor
inhibition of the striatopallidal projection in nigrostriatal dopamine-deficient mice. J Neurophysiol. 2013
Aug 14. [Epub ahead of print]PubMed PMID: 23945778.
3) Ellens DJ, Leventhal DK. Review: Electrophysiology of Basal Ganglia and Cortex in Models of
Parkinson Disease. J Parkinsons Dis. 2013 Jul 23. PubMed PMID: 23948994.
4) Fahn S; Parkinson Study Group. Does levodopa slow or hasten the rate of
Progression of Parkinson's disease? J Neurol. 2005 Oct; 252 Suppl 4:IV37-IV42.
Review. PubMed PMID: 16222436






DISCOVERY OF SMALL MOLECULE INHIBITORS FOR AURORA KINASE A USING BOTH
LIGAND AND STRUCTURE BASED DRUG DISCOVERY TECHNIQUE
K. Leena*, Arun Rasheed
Al-Shifa College of Pharmacy, Perinthalmanna, Kerala

Cancer is one of the major diseases in the human mortality and health hazard to human growth.
Aurora kinases a serine threonine kinase protein plays an important role in cell cycle and thus used as a
potential target for the treatment of cancer. Computational chemistry is one of the dynamic technologies
now being used in the drug discovery. Lot of work either by structure based or ligand based drug discovery
has been conducted. Combination of the two methods was found to be more beneficial as per the chemist
experiments & is basis of my work. In the present work, we aim to discover potential leads against Aurora
kinases using various rational methods of drug discovery. Available crystal complexes of AKs were
analyzed for their interactions and quantified them with glide-extra precision (XP) docking. About 20
proteins were selected from the PDB based on the Resolution factor, R-factor and R-value, and after docking
with the native ligands the RMSD value was calculated and the protein with least RMSD was found to be of
3UOK and used this protein for our docking studies. The native ligands were clustered based on the
structural similarity and about 9 such sets were obtained. Several energy based pharmacophore model was
generated based on the ligand receptor interactions. The hypotheses so generated are now used for virtual
screening of Asinex database. Hits were obtained which were again docked backed with the 3UOK protein,
this is to remove any false positive result and confirm their interaction with the protein. The top molecules
were taken which are having the best fitness score. Now these molecules were checked whether already
being explored or not. Different software like scifinder, pubchem & chemspider were used. Promising
molecules from the Asinex database were obtained. To check the stability of interactions made by these
molecules molecular dynamics was done.













INSILICO ANALYSIS OF ALGAL TOXIN INTERACTION WITH PROTEIN PHOSPHATASE
S.Gopinath
1
L.A.Shivaram
2
Mrs. Shobana*
SRM University, Chennai
Microcystin, a class of hepatotoxins produced by species of freshwater cyanobacteria primarily Microcystic
aeruginosa. These are cyclic nonribosomal peptide toxins, which are found, related to the incidents of
human illness and animal poisoning. In addition to their acute hepatotoxic effects, they have also been found
to act as tumor promoters. Microcystin-LR (L and R identifying the 2 variable amino acids, in this case
leucine and arginine respectively). It consists of several uncommon non-proteinogenic amino acids such as
dehydroalanine derivatives and the special -amino acid ADDA (3-Amino-9-methoxy-2, 6, 8-trimethyl-10-
phenyldeca-4, 6-diene acid). The ADDA moiety is responsible for its toxicity. The main aim is to study the
interaction of Human Protein phosphatase and microcystin and to find a better potential inhibitor against
microcystin by means of ligand based pharmacophore studies using the known ligands. Insilico analysis was
performed using Schrodinger 9.1.

Keywords: Microcystin, hepatotoxin, docking.

















Soluble epoxide hydrolase inhibitor, t-TUCB, protects against myocardial ischemic injury in vivo
Ayush Shrestha, Praveen T.K and Pooja Thomas
Department of Pharmacology, JSS College of Pharmacy, Udhagamandalam (A constituent college of JSS
University, Mysore)

Aims: To determine the protective role of a soluble epoxide hydrolase inhibitor, trans-4-{4-[3-(4-
trifluoromethoxyphenyl)-ureido] cyclohexyloxy} benzoic acid (t-TUCB), in isoproterenol (ISO)-induced
myocardial ischemic injury in vivo.
Methods and Results: Cardioprotective activity of t-TUCB was studied against ISO induced myocardial
ischemic injury in male wistar rats. Pretreatment with t-TUCB at 3, 10 and 30 mg/kg, p.o for a period of 14
days significantly prevented ISO induced changes in EKG parameters (QT
c
interval prolongation, ST height
depression, pathological Q waves formation and T wave inversion), serum cardiac biomarkers (CK-MB and
LDH), myocardial calcium levels and infarct size when compared to the untreated control animals (p< 0.05).
Docking studies for t-TUCB were carried out against human soluble epoxide hydrolase (sEH) protein (PDB
entry: 3KOO, X-ray resolution=2.7) using glide (Schrdinger suite 2012, version 9.3) to predict its binding
mode. The study results revealed that the compound formed H-bond interactions with TYR383 and TYR466
residues at the active site of sEH. Glide score obtained with this compound was -11.03 which is comparable
to the standard sEH inhibitor 24D.
Conclusion
sEH inhibitor, t-TUCB, significantly prevents isoproterenol induced myocardial ischemic injury in rats
providing a preliminary confirmation of the efficacy of t-TUCB by oral administration in rats. Also, the in
silico docking studies show that this molecule has binding mode similar to other reported inhibitors of sEH.











ROLE OF CRYSTAL WATER MOLECULES IN DOCKING STUDIES OF NATURAL
INHIBITORS TARGETING PHOSPHOTIDYLINOSITIDE-3-KINASE (PI3K) PATHWAY IN
CANCER
Pooja Sharma
1
, Aparna Shukla
1
, Feroz Khan*
1
Metabolic & Structural Biology Department, CSIR- Central Institute of Medicinal & Aromatic Plants,
Lucknow, India
E-mail: f.khan@cimap.res.in

The phosphoinositide 3-kinase (PI3K) pathway is an important signal transduction system linking oncogenes
and multiple receptor classes to many essential cellular functions including cell death and survival, cell
migration, protein synthesis and metabolism. PI3K is a most commonly activated signaling pathway in
human cancer and therefore presents both an opportunity and a challenge for cancer therapy. Water
molecules are routinely included in molecular docking studies of signaling pathway receptors because of its
important role in mediating ligand protein interactions. We studied evaluation of docking experiments both
in presence and absence of water molecules. AutoDock docking simulation results were than compared and
results showed no significant effect on docking energy and RMSD. However, an overall improvement in
binding pose prediction was achieved when selected water molecules are included during docking
experiments. This exercise provides a valuable opportunity for researchers to test their docking methods in a
blind testing environment. The improvement in the docking performance by including water molecules also
depends on protein system, chemical class of ligand, docking method and scoring function.
Keywords: PI3K, water docking, binding pose, AutoDock














Insights from molecular docking studies of anthocyanins from Syzygium cumini as potential carbonic
anhydrase II inhibitors for glaucoma
Sathyan Sri Lavvanya Priya*
Department of Biotechnology, Anna University, Regional Center, Coimbatore, Jothipuram, Coimbatore -
641 047, Tamil Nadu, India

Human carbonic anhydrase II (3KS3) is a promising drug target for glaucoma, the second leading cause of
blindness in the world. Increased ocular pressure (IOP) is the risk factor associated with glaucoma ultimately
causing lesion of optic nerves and severe visual impairment. There is no specific drug available to treat
glaucoma. Reports suggest the potential use of anthocyanins in reducing the IOP. In the present study we
refined crystal structure of 3KS3 using protein preparation wizard of the Schrodinger software. Information
for active site was obtained from literature. Three anthocyanin compounds from Syzygium cumini fruit peel
reported in our earlier work, and six existing glaucoma inhibitors were docked into the active site. Molecular
docking calculations were performed by employing Glide XP algorithm and Induced-Fit docking protocol.
Cyanidin 3,5 diglucoside showed the lowest Gscore followed by other anthocyanins and was rescored
subsequently with Prime-MMGBSA binding free energy calculations. Binding affinity of the inhibitor
indicates its efficacy in the treatment of glaucoma


















STUDY OF NOVEL MESO-SUBSTITUTED PORPHYRINS AS POTENT G-QUADRUPLEX
BINDING TELOMERASE INHIBITOR USING STRUCTURE BASED DRUG DESIGN
Rajendra Bhadane
*
, Rupali Bhadane

, Avish Maru

, Dhananjay Meshram
#

*Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Mahal, Jaipur, Rajasthan, India.

Loknete Dr. J. D. Pawar College of Pharmacy, A/P-Manur, Tal-Kalwan, Dist-Nashik, Maharashtra, India.
#
Pioneer Pharmacy Degree College, Sayajipura, Ajwa-Nimeta Road, Vadodara, Gujarat, India.

The biological significance of G-quadruplex has been recognized by numerous research efforts. With the
advancement of x-ray crystallography, CD and NMR spectroscopy studies, the structure and topology of G-
quadruplex has become clear than before. As there are many G-rich regions along chromosomes and some
of these are associated with the promoter of oncogenes. This provided us an excellent opportunity to
perform structure based drug design to target telomeric and oncogenes promoter sequences of 2A5R and
2HRI quadruplexes using series of ligand.












Binding Affinity Based Inhibitor Design for Matrix Metalloproteinases (MMP-1) by MD-
Simulation and Docking Method
Su8rata *asgupta
?
, Bishnu P. %ukhopadhyay
2-
, *eepak (. %ishra
2


1. Institute of Bioscience and Biotechnology,C.S.J.M. University, Kanpur-208024, India
2. Department of Chemistry, National Institute of Technology-Durgapur-713209, India

%%P3? 8elongs to the collagenase group o7 %atrix %etalloproteinase and is in,ol,ed in di77erent diseases e.g.
arthritis, metastasis and degradation o7 7i8rillar collagens etc. ;he en2yme is kno9n to 8e e77ecti,e in ,arious
in7lammatory and other tissue destruction diseases. #ecently %%P3? is considered as drug3target 7or di77erent
diseases. %ost o7 the inhi8itorsD*rugs are likely to 8e in,ol,ed in the interaction 9ith the En
2F
3ions! ho9e,er other
ligand 8inding pockets 5S? G SC6 are also 8eing there 9here the drug could 8ind e77ecti,ely and 8lock the protease
acti,ity. ;ill no9 7e9 inhi8itors o7 %%P3? are a,aila8le and they are under clinical trials e.g., Prinomastat,
Funalenone, #e8imastat, P</ etc. "7ter extensi,e in,estigation o7 the geometricalD electronic conse:uences o7
their interaction 9ith %%P3?, especially in some en2yme3inhi8itor complexes H3 ray structures 5P*B .*: ?@E,
?@F, ?@<, 2;< and ?/F6, 9e ha,e modeled a series o7 ne9 structural analogs 8y
addingDsu8stitutingDmodi7ying the 7unctionalDalkyl groups. ;he structure o7 those modi7ied ligands are optimi2ed
and docked in the En2yme 5using /EHDP";/DSI.SS *>( ser,ers6. ;he stereochemical :ualities o7 their 8inding
modes ha,e 8een checked 7ollo9ed 8y 2 ns %*3Simulation studies o7 their sol,ated 5adding the crystal molecules6
structures. Binding energy 5<igand3#eceptor )an der Iaals, Electrostatic, /ydrogen Bond, Sol,ation Free Energies
and on7ormational Entropy6 o7 each modi7ied ligand is calculated 58y PE"#<S ser,er6. Based on the 8inding
energy ,alues and mode o7 interaction at the catalytic pockets, 9e ha,e screened three modi7ied compounds
5Fig.?6 9hich may think to act as 8etter or potential inhi8itor 7or %%P3?. ;he drug likeness and drug score o7
B2 compound seems to 8e 8etter compare to parent and other compounds.




Homology modeling and virtual screening approaches to identify potent inhibitors of mycolic acid
methyltransferase (Mma1)

Hymavathi Veeravarapu, Krishnaiah Dasari, Kiran Kumar Mustyala, Vasavi Malkhed and Uma Vuruputuri*
Department of Chemistry, Nizam College, Osmania University, Basheerbagh,
Hyderabad, 500001, Andhra Pradesh, India.

E-mail: vuma@osmania.ac.in, vuma1957@gmail.com

Tuberculosis is a disease with devastating social and economic costs. It ranks second as the leading
cause of death from an infectious disease worldwide [1]. India is the highest TB burden country in the
world, accounting for one fifth of the global incidence [2]. The cell envelope of Mycobacterium tuberculosis
is distinctive and associated with its pathogenicity. Mycolic acids are major components of the cell wall of
M. tuberculosis [3]. Mycolic acid methyl transferase, MmaA1 is required for the introduction of methyl
group in trans-oxygenated meroacids [4] which are essential for the synthesis of Mycolic acids. In the
present study MmaA1 is targeted to identify novel inhibitors to inhibit cell wall synthesis in M. tuberculosis.
A homology based model of MmaA1 was generated using Modeller [5] and evaluated. The residues
of active site were identified by SiteMap[6], CASTp [7] and literature studies. The 3D model was subjected
to docking and virtual screening studies [8,9] using Schrodinger Molecular modeling Suite[10]. The
molecules with satisfactory ADME properties and highest docking scores are graded to design novel potent
inhibitors for MmaA1.
Keywords: Tuberculosis, Mycolic acid, Mycolic acid methyltransferase, Methyl transferase, Homology
modeling, Docking, Virtual screening.
References:
[1] WHO Global Tuberculosis Report 2012
[2] India Annual TB report 2012
[3] Kuni Takayama, Cindy Wang and Gurdyal S. Besra, Pathway to Synthesis and Processing of Mycolic
Acids in Mycobacterium tuberculosis, Clin. microbiol. Rev., 18.1.81-101.2005.







Homology modeling and Virtual Screening of Ubiquitin conjugation enzyme RV3 as a novel cancer
drug target
Vishwanath Ramatenki, Ramasree Dulapalli, Saritha Rajender Potlapally, Ragavendra Prasad U.S.H and
Uma Vuruputuri*#
*Department of Chemistry, Nizam College, Osmania University, Basheerbagh, Hyderabad - 500001.
# University College of Science, Osmania University, Hyderabad- 500007

Email ID: vuma1957@gmail.com


Cancer is one of the major health problems worldwide. The initiation and progression of cancer is caused
due to imbalance between the cell growth and programmed cell death. The imbalance in the cell number is
triggered by the ubiquitin family enzymes [1]. Ubiquitin dependent proteolysis by the 26s proteasome plays
a crucial role in cell cycle progression as well as in tumorigenesis [2]. In this pathway ubiquitin conjugation
enzyme RV3 binds to ubiquitin conjugation enzyme E2 variant 2 (E2V), to form a heterodimer. The
heterodimer (RV3-E2V) interacts with Ring finger domain and is involved in polyubiquitation reaction and
cell cycle progression[3]. The inhibition of the heterodimer formation is a target for novel cancer drug
discovery in cancer. In the present study the RV3 enzyme is targeted for designing a new antagonist against
cancer. The RV3 enzyme 3D model was generated by homology modeling technique using Modeller 9.12
programme [4]. The generated 3D-structure of the RV3 enzyme was validated, active site was identified
using various computational tools and corroborated with literature [3]. The grid was generated considering
the active site residues and virtual screening was performed using molecular databases to identify the new
leads [6]. The ADME for the molecules were predicted and identified as potential leads against RV3 enzyme
for cancer therapy.

Key words: Cancer, Ubiquitin conjugation enzyme, Virtual screening, ADME.
References:
1. Holler D and Dikic I, Targeting the ubiquitin system in cancer therapy. Nature review. 458 (2009)
438-444.
2. Fraile JM, Quesada V, Rodriguez D, Freije and Lopez-otin L, Deubiquitinases in cancer: new
functions and therapeutic options. Nature review oncogene. 31(2012) 2373-2388.
3. Trevor F. Moraes, Ross A. Edwards, Sean Mckenna, Lanolon Pastashok, Wei Xiao, J.N. Mark
Glover, and Michael J. Eilison. Crystal Structure of the human ubiquitin conjugating enzyme
complex, hMms2-hUbc13. Nature Structural Biology, 8(2001) 669-673.









Identification of novel leads against SOCS protein causing insulin resistance and type 2 diabetes- A
site directed docking and virtual screening in silico study
Ramakrishna Dumpati, Bhargavi Kondagari and Uma Vuruputuri*#
*Department of Chemistry, Nizam College, Osmania University, Basheerbagh, Hyderabad, 500001, Andhra
Pradesh, India.

# Department of Chemistry, University College of Science, O.U, Hyderabad- 500007
E-mail: vuma@osmania.ac.in
Insulin resistance is the main feature of onset and development of type 2 diabetes mellitus
1
. The cognitive
proteins in sensing the insulin and other natural substrates will become less sensitive or inert, due to over
expression of cytokine signal regulatory proteins like SOCS
2
. In view of the epidemic nature of type 2
diabetes and the substantial rate of failure of current oral anti diabetic drugs the quest for new therapeutics is
intensive
3
. In the present study, SOCSX that regulates the signalling pathway of insulin receptor with its
substrate is subjected to 3Dstructural evaluation using comparative modelling techniques
4
. Its active site is
identified by using the Schrodinger module SITE MAP
5, 6
. Protein protein docking studies were done to
identify specific docking amino acids between SOCSX and its natural substrate
7
. The protein is further
considered at this active site for virtual screening studies using Schrodinger module Glide
8
with various
databases of molecules using standard protocols
9,10
. Novel molecules against SOCSX are identified, which
may proveto be potent insulin resistance therapeutics.
Key words: Insulin resistance, anti-diabetic, comparative modeling, protein-protein docking

References
1. Roy Taylor,(2012), Insulin Resistance and Type 2 Diabetes, Diabetes, 61, 4, 778- 779.
2. Danielle L. Krebs and Douglas J. Hilton, (2003), A New Role for SOCS in Insulin Action, sciences
stke, pe6, 1-3.
3. Saenz A, Fernandez-Esteban I, Mataix A, Ausejo M, Roque M, Moher D, (2005), Metformin
monotherapy for type 2 diabetes mellitus, Cochrane Database of systemic Reviews, 20, 3.
4. N. Eswar, M. A. Marti-Renom, B. Webb, M. S. Madhusudhan, D. Eramian, M. Shen, U. Pieper, A.
Sali, (2006), Comparative Protein Structure Modelling With MODELLER, Current Protocols in
Bioinformatics, Supplement 15, 5.6.1-5.6.30.
5. Halgren TA. (2000), Identifying and characterizing binding sites and assessing druggability. Journal
of Chemical Information and Modelling, 49, 377-389.





Multiple Docking Strategies, Prime/MMGBSA Calculations and Molecular Dynamics Simulations
for Lead Discovery against Leptospira interrogans

Dibyabhaba Pradhan*, Vani Priyadarshini, Manne Munikumar, Sandeep Swargam and Amineni
Umamaheswari**
Bioinformatics Centre, Sri Venkateswara Institute of Medical Science University, Tirupati, Andhra Pradesh
517507
Email: svims.btisnet@nic.in

Discovery of novel lead molecules based on potent drug targets of Leptospira interrogans, the causative
pathogen of human leptospirosis, is of significant research interest. Lipopolysaccharide (LPS) layer prevents
entry of hydrophobic agents into the cell and protect the bacterium. UDP-3-O-[3-hydroxymyristoyl] N-
acetyl glucosamine deacetylase (LpxC) catalyzes second step in lipid A biosynthesis which anchors LPS
into the membrane of Leptospira. LpxC was identified as a common potential drug target among Leptospira
interrogans serovars through subtractive genomic approach, metabolic pathway analysis and comparative
protein sequence analysis (Amineni et al., 2010). A reliable three dimensional (3D) structure of LpxC by
incorporating inhibitor, BB-78485 into active site was generated based on 2VES using Modeller (Pradhan et
al., 2013). More than one million 2D compounds of LigandInfo database were utilized to set up an in-house
database of 3D compounds using PHASEv3.4. 3D structures of substrate UDP-3-O-[3-hydroxymyristoyl]
N-acetyl glucosamine and eight known LpxC inhibitors were prepared using LigPrep. Structural analogs for
the substrate and inhibitors were searched from the in-house ligand database using shape screening module
of PHASE. A ligand dataset of 4050 compounds obtained from 3D structural analog search along with
substrate and eight inhibitors were docked into LpxC active site through three stage docking techniques
[high throughput virtual screening, standard precision and extra precision (XP)] using Glidev5.7. Ten top
ranked compounds were re-docked using quantum polarized ligand docking (QPLD) and induced fit
docking (IFD). Prime/MMGBSA Calculations were performed for LpxC-lead complexes obtained in XP,
QPLD and IFD. Lead1 was identified as the best lead in three docking methods and subsequent Prime/MM
GBSA calculations. The lead1 showed favorable molecular interactions with active site residues. Molecular
dynamics simulations of LpxC and lead1 docking complex for 10 ns revealed that the complex remained
stable and reproduced docking interactions in the system closer to physiological environmental conditions.
Therefore, lead1 was proposed as potential inhibitor LpxC of Leptospira interrogans.

References
Amineni, U., Pradhan, D., & Marisetty, H. (2010). In silico identification of common putative drug targets
in Leptospira interrogans. J Chem Biol 3, 165173.









Homology modeling and docking analysis of RNA chaperone Hfq in Haemophilus influenzae R2866
involved in pathogenesis.

Money Gupta
1*
, Shubani Chokara
1*
, Nitin Rai
1
, Vallari Saxena
1
, Monikankana Deka
1
, Chakresh Kumar
Jain
#1
1
Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, NOIDA, UP,
India -201307

E-Mail: ckj5222yahoo.com,

RNA chaperone (Hfq) has been recently reported to be involved in the emergence of pathogenesis, caused
by an opportunistic pathogen, Haemophilus influenzae R2866. It is primarily involved in controlling the
gene expression, important to adjust stress conditions and virulent factors within the host organism.
Understanding the mechanism of pathogenesis by RNA chaperone (Hfq) and finding the suitable inhibitors,
is an upcoming challenge.
To address the above issue, we have predicted its homology based three dimensional structure of 91 amino
acid protein in this study using MODELLER 9.11. The predicted Protein model was validated using
PROCHECK, ProSA, ERRAT, VERIFY-3D and WHATIF. The molecular dynamic simulations performed
using GROMACS 4.5.5 further confirmed the stability and the compactness of the predicted homology
model (300K and 1 bar). We have performed the docking experiment using Autodock (Vina) on acridone
based inhibitor 8a and 1, 25-dihydroxy-23-oxo-vitamin D3 along with other verified chaperone inhibitors
and analyzed the effectiveness of these two drugs against RNA chaperone (Hfq) from that of already
existing chaperone inhibitors. Docking analysis reveal that acridone based inhibitor 8a and 1, 25-dihydroxy-
23-oxo-vitamin D3 have shown better binding energy i.e. -7.4 kcal/mol and -7.3 kcal/mol respectively, as
compared to the already existing chaperone inhibitors 6-aminophenanthridine, NVP-AUY922 and radiciol
which showed binding energy of -6.2 kcal/mol, -6.5kcal/mol and -6.8kcal/mol respectively.Inhibition of
RNA chaperone (Hfq) may lead to inability of Haemophilus influenzae R2866 to survive under stressful
conditions and to regulate virulence associated genes. Hence, we can hypothesize that these two compounds
may be effective in dealing with many diseases caused by this human pathogen.

Keywords: RNA chaperone (Hfq), Modeller 9.11, Autodock (Vina), GROMACS 4.5.5 and Haemophilus
influenzae R2866.

References:
1. Hempel RJ, Morton DJ, Seale TW, Whitby PW and Stul TL (2013) The role of the RNA chaperone Hfq
in Haemophilus influenzae pathogenesis. BMC Microbiology 13:134.
2. Trott O and Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new
scoring function, efficient optimization and multithreading. J Comput Chem 31:455-461.
3.Fiser A and Sali A (2003) Modeller: generation and refinement of homology-based protein structure
models. Meth Enzymol 374: 46191.
4.Hess B, Kutzner C, Van Der Spoel D and Lindahl E (2008) GROMACS 4: algorithms for highly efficient,
load-balanced, and scalable molecular simulation. J Chem Theory Comput 4:435-447.










Insilico and invitro antimycobacterial screening of 3,4 dihydro pyrimidones

N.Gopinathan
a
*,Dr.K.Chitra
a
, Dr.K.Lakshmi
b
, Dr.A.Purnima
c


a-Department of Pharmaceutical Chemistry, Faculty Of Pharmacy, Sri Ramachandra University, porur,
Chennai-600116
b-Dean, SRM College Of Pharmacy, Kattankulathur, Chennai.
c-Department Of Pharmacology, K.L.E. Universitys College Of Pharmacy, Bangalore.



Based on bioisosteric similarities with 5-flurouracil, a series of 5-(1H-benzimidazol-2-yl)-4-(1H-
indol-3-yl)-6-methyl-3,4-dihydropyrimidine-2(1H)-one and thione derivatives have been designed. The
target compounds have been synthesized by multi component reaction which involves one-pot organic
reactions using Ethylacetoacetate, urea/thio urea and aryl aldehydes in presence of HCl/H
2
SO
4
by
conventional method. Molecular docking of the target compounds into the enzyme Mycobacterium
tuberculosis enoyl reductase (InhA) revealed important structural information on the plausible binding
interactions. Binding poses of the all the compounds were energetically favorable and showed good
interactions with the active site residues. Few selected compounds were also evaluated for antitubercular
activity in vitro against drug-sensitive M. tuberculosis strain by luciferase reporter phage (LRP) assay
method. Luciferase reporter phage (LRP) assay InhA, the enoyl acyl carrier protein reductase is one of the
key enzymes involved in the type II fatty acid biosynthesis pathway of M. tuberculosis. The results have
shown that derivatives were proved to be highly potent inhibitors against Mycobacterium tuberculosis enoyl
acyl carrier protein reductase. Glide software of Schrdinger was used to carry out the current work.

















Molecular modeling and identification of glucokinase activators through molecule docking and
molecular dynamics simulations
Pabitra Mohan Behera
1
, Deepak Kumar Behera
1
, Sanghamitra Nayak
1
, Anshuman Dixit
2
and Payodhar
Padhi
3

1 Centre of Biotechnology, Siksha O Anusandhan University, Bhubaneswar, Odisha, Pin-751030, India
2 Department of Translational Research and Technology Development, Institute of Life Sciences, Nalco
Square, Bhubaneswar, Odisha, PIN-751005, India
3 Hi-Tech Research and Development Centre, Konark Institute of Science and Technology, Techno Park,
Jatni, Bhubaneswar, Odisha, PIN-752050 India
E-mail: uniquepabs@gmail.com

The glucose phosphorylating enzyme glucokinase (GK) is a 50kD monomeric protein having 465 amino
acids. It maintains the glucose homeostasis inside cells, acting as a glucose sensor in pancreatic -cells and
as a rate controlling enzyme for hepatic glucose clearance and glycogen synthesis. The 3D structure has two
crevices, one for the active site, binding D-glucose and the other for a putative allosteric activator named
glucokinase activator (GKA). The glucokinase activators (GKAs) interact with the same regions of the GK
enzyme that is commonly affected by naturally occurring mutations in humans but most GKAs dont bind to
GK in the absence of glucose. Mutations of the GKAs interacting residues lead to activation of GK.

We present the molecular modeling studies of 4 natural variant of hepatic GK with a single template 4IXC
complexed with both glucose and an activator 1JD. These variants are important as they lie in the allosteric
site. In order to explore the flexibility of the allosteric site, a 10ns molecular dynamics simulation was done
on each of the modeled variant. Subsequently, a group of molecules (total 186) were docked into the
conformational ensembles of the variants allosteric site to identify the molecules which can bind to
different site conformations.








Structural, evolutionary and interaction studies of Huntingtin (HTT), a candidate
Huntington protein and its association with Kalirin
Saranya Jayapalan and Jeyakumar Natarajan*
Data mining and Text mining Laboratory, Department of Bioinformatics, Bharathiar University,
Coimbatore- 641046.
Huntington disease (HD) is one of the most common autosomal- dominant neurodegenerative
disorder caused by the expansion of CAG repeats in HTT gene resulting in a polyglutamine tract near to the
amino terminus of the huntingtin protein (HTT). Kalirin is HTT binding serine/threonine protein kinase
which is involved in association with Huntingtons disease. Structural information of Kalirin HTT
complex is being absent. We resorted into the molecular modeling of kalirin protein for gaining the insight
into the mechanism of its association in HD. The evolutionary history of HTT and Kalirin proteins were
constructed, human amino acid sequences are conserved with other three hominoid genomes such as
chimpanzee, gorilla and orangutan using bootstrap value based on 1000 replications. Molecular docking
analysis was employed to elucidate the binding mode of the ligand complex for HTT. The docking
experiment demonstrated that HTT is involved in major polar but charged and non-polar hydrophobic amino
acid residues. The molecular docking and interaction studies of HTT and Kalirin were performed to infer the
implications in HD. The overall studies suggest a baseline for the design, developmental and validation of
novel drugs against HD and aids in elucidating the ancestral relationship for the prediction of protein
function and family.
Keywords: Huntingtons disease, HTT, Kalirin, docking, evolutionary












Chorismate synthase from Plasmodium falciparum: A novel target for anti-malaria drug discovery
Satya Tapas*, Shailly Tomar
#
and Pravindra Kumar
#
.
* Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
# Department of Biotechnology, Indian Institute of Technology, Roorkee, India.


The enzymes of shikimate pathway in Plasmodium falciparum are potent targets for designing novel anti-
parasitic agents for the treatment of malaria. Chorismate synthase (CS) is a key enzyme in the shikimate
pathway which catalyzes the seventh and final step of the pathway. P. falciparum chorismate synthase
(PfCS) is unique in terms of enzymatic behaviour, cellular localization and in having two additional amino
acid inserts compared to any other CS. In present work, the structure of PfCS along with cofactor FMN was
predicted by comparative homology modeling using crystal structure of Helicobacter pylori chorismate
synthase (HpCS). The quality of the model was validated using various structure analysis servers and
molecular dynamics. Dimeric form is the functional unit of CS where interface of two monomers contribute
to FMN binding pocket. Thus, dimeric form of PfCS was generated to identify key residues those contribute
to dimeric interface and FMN binding pocket. Further, FMN binding mechanism involving movement of
loop near active site was proposed. Active site pocket was identified and substrate 5-enolpyruvylshikimate
3-phosphate (EPSP) was docked into it using GLIDE docking software version 5.5 (Schrdinger). Further,
various EPSP analogs available in PubChem database as well as the previously reported inhibitors were
docked into active site to identify potent inhibitory agent using AUTODOCK 4 and GLIDE 5.5. The
predicted binding efficiency of retrieved analogs was estimated based on the values of dissociation constant
Ki, docking score, docking energy and extent of interactions with active site residues. The comparative
study of eight different analogs with highest predicted binding efficiency into active site of PfCS and HpCS
was established. The study resulted in identification of putative inhibitors of PfCS with binding efficiency in
nano-molar range. The selected putative inhibitors could lead to the development of anti-malarial drugs.













In silico Approach to Construct non mutant Peptide Sequence for HIV GP 120 and validation
confirmed in Docking studies
Sumeet R. Deshmukh, Minesh Jethwa, Pritee Chunarkar and Md Ataul Islam
*
Department of Bioinformatics, Rajiv Gandhi Institute of Information Technology and Biotechnology,
Bharati Vidyapeeth Deemed University, Pune-Satara Road, Pune 411 043

Email: ataul.islam80@gmail.com


As per review of literature, an envelope protein precursor, GP 160 of HIV is encoded by env gene.
Spontaneous mutation has been observed in this gene, ultimately causing conformational changes in GP120.
GP 120 serves as target site for ligand binding for most of the available drugs. This domain remains
unrevealed to study conformational changes in the protein. The Aim was to come up with novel peptide
sequence which will represent mutant GP120. The peptide sequences are validated with docking studies
carried out by Schrodinger 2013 package and results were discussed which will help to trigger binding
affinity with all mutant strains of HIV1. PERL script was developed to construct the peptide sequence by
using two different approaches. In first approach multiple aligned sequences of GP120 obtained from
clustalW were used to develop peptide sequence. The aligned sequences were then used to find out
frequency of each amino acid for each position within the sequences. In another approach fasta sequences of
GP120 were used to develop peptide sequence. Further 3D structure were predicted by modeller. Further
validation of each structures and molecular docking are to be taken in consideration.














Polarized docking of Peptide inhibitors on the envelope glycoprotein of Dengue virus
J. Asnet Mary
1
, R. Shenbagarathai
2


1. Department of Zoology, Fatima College, Madurai, Tamil Nadu, India
2. PG and Research Department of Zoology and Biotechnology, Lady Doak College, Madurai, Tamil Nadu,
India.

Dengue virus is a major public health problem in tropical and subtropical area. The envelope
glycoprotein of dengue virus mediates the entry into cells by fusion between viral membrane and host
membrane. It is a potential target for a drug designing as it is important to instigate dengue viral infection.
Molecular docking is generally a multistep process which involves the prediction of the ligand conformation
and orientation within the targeted binding site. A comparative docking was performed with the peptide
inhibitors to observe the role of polarized docking compared to glide docking. Three tetrapeptides from the
envelope glycoprotein itself were built and docked to predict the binding affinity in place of -OG. There is
a significant difference observed in the docking score in polarized docking and it has increased the number
of hydrogen bonding due to polarization.
















Acetyl cholinesterase inhibition of thienopyridines: in silico and in vivo studies
V. Manasa, T. Ganapathi, P. Swathi, A. Rajasekhar Reddy, K. Umasankar, B. Shireesha*
Medicinal Chemistry Research Division, Department of Pharmaceutical Chemistry, Vaagdevi College of
Pharmacy, Waragal-506001, A.P, India;
E. Mail: sirimedchem@gmail.com


Alzheimers disease is a chronic neurodegenerative disease characterized by brain atrophy, loss of
neurons and loss of synaptic function. Aging is considered the major risk factor of AD, which is
characterized pathologically by the accumulation of beta amyloid peptides and neurofibrillary tangles as
well as increased levels of acetyl cholinesterase.

The present study was designed to perform docking studies to identify the nature and amount of
interactions of the series of ten thienopyridines (BN-4, BN-5, BN-6, BN-7, BN-8, BN-13, BN-14, BN-15,
BN-16, BN-17) with Torpedo acetylcholinesterase (1ACJ) and found good binding interactions with the
active site. In a complex with tacrine, the active site consists of amino acids viz., Trp-84, Trp-279 and Phe-
330. Perusal of MolDock scores and ReRank scores of molecules shows potency of BN-4, BN-14 and BN-
16 with ReRank scores of -101.04, -104.70 and -112.87 respectively. Validation of docking studies were
also performed by evaluating thienopyridines for the acetylcholine esterase inhibition using scopolamine
induced amnesia in male albino mice for the treatment of Alzheimers disease. In the series, BN-4, BN-14
and BN-16 showed significant effect when compared to tacrine by significantly inhibiting the acetyl
cholinesterase levels which were initially enhanced by the treatment of scopolamine when compared to
control group.















DESIGNING OF NOVEL SMALL MOLECULES FOR THE TREATMENT OF INFLAMMATORY
DISEASE: AN IN SILICO APPROACH
Chethan G H* and Amol B Khade
Manipal College of Pharmaceutical Sciences, Manipal University, Manipal


Nitric oxide (NO) is an important mediator synthesized by many types of cells in different tissues and is
involved in many physiological and pathological responses. iNOS, an isoform of Nitric Oxide synthase
which is activated by various immunological stimuli generates overproduction of NO which modulates
inflammation through various pathways and plays an important role in the regulation of immune reactions
and also been implicated in various pathological responses such as tissue damage, rheumatoid arthritis,
ischemia, cell apoptosis and onset of colitis. Blocking the excessive production of NO by inhibiting iNOS
has been proven to be efficacious in reducing inflammation and treating these associated diseases.
In the present study small molecules have been designed virtually and screened in silico to predict their
inhibitory potential on iNOS for the treatment of inflammatory disease. Based on the hit structure that has
been reported in literature against the inhibition of iNOS, we report the new possible potential inhibitors of
iNOS which have the similar scaffold of the hit structures. The virtually designed small molecules were
docked into the active site of iNOS. The docking of the ligands with target protein was performed using the
free evaluation licence of Schrodinger software. The best molecule showed the docking score of -4.1 and
had an interaction with HEME 901, HOH 917 and HOH 1067. Further various in silico methods are
followed for predicting drug likeness, toxicity and ADME parameters to sort out the best molecule. A
rational design described in this work may be further used to develop the small molecule inhibitor of iNOS
for the treatment of inflammatory disease.
Key Words: iNOS, Inflammation, in silico design and glide docking












&irtual 'creening of in(i)itory Indian p(ytoc(emicals against !uman *!+*! for ,(eumatoid art(ritis
Poorani.B, Sucharita.%, Priya S9aminathan-
Department of Bioinformatics, S2M University
Email:sucharita.muthus9amy@gmail.com
*ihydroorotate dehydrogenase J*/>*/K is an F%$ 7la,oprotein en2yme in mitochondria that catalyses the 7ourth
step in the %e novo 8iosynthesis o7 pyrimidine. .t con,erts dihydroorotate to orotate. */>*/ inhi8ition results in
8ene7icial immunosuppressant and antiproli7erati,e e77ects in diseases such as rheumatoid arthritis. ;he anti3
in7lammatory drug <e7lunomide has 8een sho9n to inhi8it */>*/. /uman */>*/ has t9o domains: an alphaD8eta3
8arrel domain containing the acti,e site and an alpha3helical domain that 7orms the opening o7 a tunnel leading to
the acti,e site. <e7lunomide has 8een sho9n to 8ind in this tunnel. But it has many side e77ects. %ost serious is
symptomatic li,er damage ranging 7rom Laundice to hepatitis, 9hich can 8e 7ulminant, se,ere li,er necrosis, and li,er
cirrhosis and interstitial lung disease . ;here are medicinal plants 9ith signi7icant ad,antages can 8e used 7or the
treatment o7 rheumatoid arthritis. .n this paper 9e ha,e tried to explore ,arious .ndian medicinal her8s that 7or
ages ha,e 8een used as a treatment 7or rheumatoid arthritis. Ie collected a num8er o7 acti,e ingredients o7
traditionally used .ndian medicinal plants against #heumatoid arthritis 7rom literature. ;hese compounds 9ere
,irtually screened against /uman */>*/. ;he hits o8tained 9ere then indi,idually docked to the receptor and
compared 9ith the <e7lunomide docking. ;hose compounds that sho9 a higher @lide score 9as checked 7or drug
lika8ility properties using 1ikprop. ;he results suggest a list o7 compounds that can 8e 7urther analy2ed and
optimi2ed to 7ind a rational alternati,e 7or treating #heumatoid arthritis.
Keywords: DHODH, Rheumatoid arthritis, Virtual Screening, Anti-inflammatory, Drug likability.













Docking study of betalains with HIF prolyl 4-hydroxylase enzyme
Sanjay P. Chauhan *, Jagat R. Upadhyay, B. N. Suhagia
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Dharmsinh Desai University, Nadiad,
Gujarat
E-mail: sanjulmcp@rediffmail.com

Beet root is traditionally used as nutritional supplement in anemia. Major chemical constituents of beet root
are betalain class of compounds. Betalains are accepted as anti-oxidants and they may be responsible for
stimulating erythropoesis. HIF prolyl 4-hydroxylases (PHD) are a family of enzymes that mediate key
physiological hypoxic responses such as erythropoietin (epo) secretion and erythropoiesis. Many synthetic
inhibitors are designed with the aid of ligand- and structure-based methods that inhibit PHD and stimulate
erythropoietin secretion. Objective of the present study is to explore interactions of betalains with PHD.
Betalains (Betanin, Isobetanin, Neobatanin and Indicaxanthin) and literature reported synthetic PHD
inhibitors were docked into active site of HIF-hydroxylase using FRED docking tool from Open Eye
Scientific Inc. Docking simulation reveals chelation of ferrous ion, hydrogen bonding and hydrophobic
interactions of betalains with PHD. Betalains were found to interact with different amino acid residue of the
PHD in the same manner as synthetic inhibitors. Based on docking simulations, betalains may inhibit HIF
prolyl 4-hydroxylase and stimulate erythropoesis.
















In Silico Study of Active Site of Helicobacter pylori Urease and its Inhibition by Hydroxamic Acid and
its Analogues
Richa Arora & Rita Kakkar*
Computational Chemistry Group, Department of Chemistry, University of Delhi, Delhi, India
E-mail: rkakkar@chemistry.du.ac.in

Urease catalyzes the hydrolysis of urea to ammonia and carbamate in plants, algae, fungi and several micro-
organisms. This activity of urease is responsible for pathologies caused by Helicobacter pylori by allowing
it to survive at the low pH in the stomach. Various studies have been conducted on different class of
inhibitors of urease, out of which hydroxamic acids emerged as promising candidates. To understand the
mechanism of inhibition of urease by hydroxamic acids, we have quantum mechanically studied in detail the
active site of Helicobacter pylori urease complexed with acetohydroxamic acid. Helicobacter pylori urease
comprises two highly electrophilic Ni(II) centers, which are responsible for appreciable charge transfer from
the nucleophilic oxygen centers of the hydroxamate ligand to the Ni(II) centers when it binds the active site.
Hydroxamic acids are strong inhibitors of urease due to their chelating ability. Therefore, a diverse library of
ligands having the hydroxamate moiety was prepared and docked into the active site of urease using the
QM/MM methodology. It was found that hydroxamic acids with hydrophobic group attached to them are
potent inhibitors of urease because they can easily penetrate the hydrophobic environment surrounding the
active site. The CONHO
-
moiety of hydroxamic acid was found to be absolutely necessary for chelation
and inhibition of urease. Our results are well in agreement with the experimental findings. Apart from the
active site residues, His 221 and Ala 365 are also important for binding of the inhibitor to the urease active
site.











Database collection
2.5 lakhs of molecules
47 molecules
28 molecules
5
molecules
Virtual screening of pyridines targeting tau protein for the treatment of Alzheimers
disease
B. Srikanth, Ch. Narsaiah, S. Divya, A. Rajasekhar Reddy, K. Umasankar, B. Shireesha*
Medicinal Chemistry Research Division, Department of Pharmaceutical Chemistry, Vaagdevi College of
Pharmacy, Warangal-506001, A.P, India

E -mail: sirimedchem@gmail.com

Virtual screening has emerged as a reliable, cost-effective and time-saving technique for the discovery of
lead compounds. Zinc is a free, web-accessible database constructed with docking, substructure searching
and compound purchasing. In zinc, molecules have been assigned biologically relevant protonation states
and are annotated with properties such as molecular weight, calculated logP and number of rotatable bonds.
Initially the database was screened for the molecules with molecular weight<450, H-donors<3, H-
acceptors<7, number of rotatable bonds<8, polar surface
area, 60-70 , clogP<5, which are found to be optimum
parameters for CNS agents. A prediction of biological
activity spectra for selected 47 compounds was performed
by PASS online out of which 28 molecules were selected
based on their Alzheimers activity (P
a
values). After
initial screening of the compounds, the tau aggregation
was considered as best target and used for further analysis.
In the present investigation, an attempt was made to
understand the ligand-receptor interactions of selected 28
molecules against human tau protein kinase as a target
enzyme, by performing docking studies using Molegro
Virtual Docker (MVD). Top 5 ligands in docking studies
were considered for synthesis and evaluation against tau
protein.

Fig. No. of molecules considered at each step of
screening









OPTIMIZATION OF BENZOTHIAZINONES AS ANTITUBERCULAR AGENT & VIRTUAL
SCREENING OF CHEMICAL DATABASES FOR NOVEL DprE1 INHIBITORS
Faizal PK, Sachchidanand
National Institute of pharmaceutical Education & Research (NIPER) Hajipur
E-Mail: faizalpk86@gmail.com, sachchi@gmail.com

Benzothiazinones (BTZs) are new class of antitubercular drugs with nanomolar bactericidal activity
that acts covalently with novel target decaprenylphosphoryl- -D-ribofuranose 2-oxidase (DprE1). In the
present study benzothiazinones, as antitubercular agents were optimized by rational drug design. Virtual
screening on DprE1 (PDB- 4FDO, 4FDN, 4F4Q) was performed in order to find novel inhibitors. Chemical
library used include Asinex Biodesign & Asinex Platinum commercial databases. The compounds which are
screened by structure-based virtual screening are re-ranked further by ligand-based screening using ROCS.
Ranking of molecule was done based on TanimotoCombo score. If the molecule belongs to first 25 or 50
molecules in both structure-based virtual screening output & ROCS output (ligand-based virtual screening)
then it was considered as potential in silico hits for testing of novel inhibitor. In the present study it was
found that one conserved water molecule close to the active site play a key role in the ligand binding. The
nitro group of benzothiazinones may cause toxicity thus it can be modified as a thiol group which can be
administered as a prodrug. Thermodynamic stability of conserved water molecule was determined using
SZMAP and found to be thermodynamically stable













IN SILICO MOLECULAR MODELING OF NEURAMINIDASE INHIBITORS AND DOCKING
STUDIES OF ANTI-FLU AGENTS

B. Akhil, N. Hari Krishna, R. Narendra, Naresh Panigrahi, V. Suresh Babu, Padilam Suresh

GITAM Institute of Pharmacy, GITAM University, Rushikonda, Visakhapatnam-530045


Neuraminidase is an enzyme present on the surface of influenza viruses, which infects human beings by
cleaving the sialic acid (N-acetyl neuraminic acid) receptors present on red blood cells. It breaks the alpha-
ketosidic linkage between terminal sialic acid and adjacent saccharide. This enables the virus to penetrate
mucosal secretions that are rich in sialic acid, and affects the respiratory epithelium leading to Influenza
(flu). Oseltamivir and Zanamivir are the new anti-virals which are invented by changing the functional
group on older drugs to reduce the drug resistance and change their reactivity with influenza virus. The
primary goal of this study was to investigate the detail interactions of some selected therapeutically useful
anti-flu agents. In silico docking studies were carried out using Glide molecular modeling software. The
RMSD between the predicted conformation and the observed X-ray crystallographic conformation of
compound equaled 0.8 by Glide indicates the reliability of the docking method. A series of anti-flu agents
belonging to the class of Pyrrolidine, Zanamivir analogues, p-aminosalicylic acid derivatives, acyl-thiourea
derivatives , thiadiazolo [2,3-a] pyrimidine derivatives, guanidinobenzoic acid inhibitors and thiazolidine-4-
carboxylic acid derivatives were docked in the binding pocket in core pocket of neuraminidase PDB ID
2HU4. Out of these the pyrrolidines and zanamivir derivatives have shown highest docking scores and from
these studies we reveal that modification of such type of compounds will lead to discovery of potent
compounds.

Keywords: Neuraminidase, Oseltamivir, Zanamivir, Docking score, IC
50
, root mean square deviations
(RMSD).



















In silico Virtual Screening of Antiepilepsy Molecules To Inhibit AMPA

Akshaya Yathish Poonja
a
, Jyothsna Pais
a
, Karthik D Hegde
a

a
Department of Biotechnology engineering, N.M.A.M. Institute of technology, Nitte, Karkala, Udupi-574
110, Karnataka, India., *All the authors equally contributed for the study.


Epilepsy has afflicted human beings since the dawn of our species and has been recognized since the
earliest medical writings. It is known that epilepsy commonly called as epilepsies is a group of disorders that
occurs as a result of seizures that temporarily impair brain function. Although there are drugs available to
treat epilepsy, screening method is needed to find promising candidates from the vast number of natural and
synthetic compounds available for epilepsy and to ensure whether the drug molecule produces an
appropriate biochemical or cellular effect. In that concern current study is aimed at screening of some
proposed drugs for neurodegenerative disorders as potent anti epilepsy drugs. In connection to that, in the
study virtual screening method is adapted and the molecules were screened through pharmacokinetic and
pharmacodynamics analysis. The study concludes four molecules such as physostigmine ,trihexyphenidyl,
benzodiazepine and carbidopa as a putative drugs for epilepsy.

Keywords: Epilepsy; Virtual Screening; Pharmacokinetics; Pharmacodynamics and AMPA











High-Throughput Virtual Screening of Pyrimidine Derivatives Against Alanine Racemase from
Streptococcus Pneumoniae
Amit M. Pant,
*


Rupesh V. Chikhale, Sunil S. Menghani and Pramod B. Khedekar

University Department of Pharmaceutical Sciences
Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur- 440 033

The term broad-spectrum antibiotic refers to an antibiotic that acts against a wide range of disease-
causing bacteria. Even if drug molecules are intended to interact with specific targets in a desirable manner,
they are often found to bind to other targets. Nowadays, research is focused on a single molecule that
simultaneously targets multiple disease causing proteins. Therefore, off-target identification of existing
chemical space can be a valuable tool to find safe and effective multi-targeted therapeutic agents at a
significantly lower cost to patients. Pyrimidines represent a class of compounds possessing diverse range of
biological activities including antineoplastic, antiviral, antibacterial, antithyroid, anti-inflamatory,
antihypertensive, sedative, CNS stimulant

action. The aim of the current study was to explore untapped
potential of various pyrimidine libraries against alanine racemase from streptococcus pneumoniae. A library
of pyrimidine derivatives was screened based on their predicted ADME parameters. The protein molecule
was prepared by homology modelling and incorporating the missing active Lys40 residue which was further
compared with the available crystal structure. The filtered compounds were then carried forward for docking
analysis against alanine racemase from streptococcus pneumoniae. Here we propose potential inhibitors
specifically interacting on, the active site, the dimer interface, and the active site entryway. Those molecules
showing interaction with some of the residues from Tyr282, Tyr352, Arg307, Ile350, Arg288, Asp170,
that are involved in dimer interface as well as active entryway or the residues from Lys40 and Tyr263 that
involved in catalysis. The proposed molecule AMP-18a shows best hydrogen bond interaction from the
screened library.










Docking and ADME studies on Indole glucosinolates as Protein-Tyrosine Phosphatase 1B (PTP1B)
and Glycogen synthase kinase -3 (GSK-3) inhibitor against Type 2 diabetes mellitus
Poornima Jayakumar, S.Mirunalini*
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University,
Annamalainagar 608 002, Tamilnadu, India

E.mail: mirunasankar@ gmail.com.


The global epidemic of obesity and type 2 diabetes mellitus have heightened the need to understand the
mechanisms that contribute to its pathogenesis and also to design and trial novel treatments using
phytochemicals is still challenging for the medical system. Docking studies have been undertaken to gain
insight into the binding mode of the investigated compounds indole-3-carbinol (I3C) and its metabolite 3,
3- diindolylmethane (DIM) which is present in vegetables, particularly members of the genus Brassica, at
the active site of targets taken. The present work aims on molecular docking analysis of the proteins,
Protein-Tyrosine Phosphatase 1B (PTP1B) and Glycogen synthase kinase-3 (GSK-3) against a indole
glucosinolates compounds I3C and DIM. Human PTP1B structure (pdb id: 4I8N) and GSK-3 (pdb id:
4IQ6) were taken from protein data bank. Docking studies were performed by Glide software (Schrdinger).
PTP1B and GSK-3 protein and inhibitors were energy minimized and Induced Fit Docking studies were
carried out for these structures. In the present study to enhance its pharmacological properties I3C and DIM
were undergo ADMEToxicity prediction (absorption, distribution, metabolism, and toxicity) to evaluate its
pharmacological properties to be an orally active compound. QikProp was used to predict the ADME/TOX
properties and Lipinski rules for these compounds. From the docking studies we obtain high docking score
and glide energy for DIM when compared to I3C also the interactions with the active site of the targets
explain the potent inhibitor activity of DIM when compared to I3C, ADME/TOX properties also supports
this study.
Keywords: Type 2 diabetes mellitus, docking, I3C, DIM, glide energy, glide score.









VSTIP: Virtual Screening Tools in Integrated Platform
Kumari, Anchala, Chakraborti, Pratim.
Apt Software Avenues Pvt Ltd, City Centre, Salt Lake Kolkata 700 064
E-mail: pratimc@adept-software.com,anchu.chy@gmail.com

Virtual screening (in-silico) methods have been developed and widely applied to pharmacology hypothesis
development and testing. These in-silico methods include database searching, quantitative structure-activity
relationships (QSAR), similarity searching, pharmacophore identification, homology modeling and other
molecular modeling procedures, machine learning, data mining, network analysis and data analysis that use
computational resources. Such methods have seen frequent use in the discovery and optimization of novel
molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and
toxicity (ADMET) properties as well as physicochemical characterization. At present the virtual screening
of lead compounds using molecular docking and pharmacophore detection are important tools in drug
discovery. Virtual screening tasks typically require a combination of several software tools and a molecular
graphics system. Thus, the integration of all the necessary tools on a single platform will enable a researcher
to access the resources through a single user friendly interface and could reduce the complexity of using
different tools for virtual screening experiments. Thus we present a software application and an integrated
platform for the management of virtual screening tools. This software application, abbreviated as VSTIP,
Viitual Screening in Integrated Platform, brings forth the virtual screening tools, available till date in a
single platform using Internet technologies. It seamlessly integrates all the available federated resources for
virtual screening leading to drug discovery in a user-friendly manner. This application represents a rich
repository of federated resources that are freely accessible, ready to use, and each of them have been
subjected to rigorous peer review. The platform provides an alternative manner to perform comprehensive
search for virtual screening tools from a list of federated resources curated thereof.
Perl, HTML, Javascript, Mysql and Apache has been used to develop this application. We intend to extend
the application in terms of seamless semantic pipeline, virtual screening sessions and so on.











Prioritizing the anticancer properties of curcumin by computer aided virtual screening and molecular
docking

Arpitha Badarinath Mahajanakatti
1
, Narasimha Sharma
1,
, Sinosh Skariyachan
1*

1
R & D Center, Department of Biotechnology, Dayananda Sagar College of Engineering, Bangalore, India

Infosys,

Chennai, India
E-mail: sinoshskariya@gmail.com

Various types of cancer accounts for 10% of total death worldwide which necessitates better
therapeutic strategies. Curcumin, a curcuminoid present in Curcuma longa, shown to exhibit antioxidant,
anti-inflammatory and anticarcinogenic properties. Present study, we aimed to analyze inhibitory properties
of curcumin towards virulent proteins for various cancers by computer aided virtual screening. Based on
literature studies, twenty two receptors were selected which have critical virulent functions in various
cancer. The binding efficiencies of curcumin towards selected targets were studied by molecular docking.
Out of all, curcumin showed best results towards epidermal growth factor (EGF), virulent protein of gastric
cancer; glutathione-S-transferase Pi gene (GST-PI), virulent protein for prostate cancer; platelet-derived
growth factor alpha (PDGFA), virulent protein for mesothelioma and glioma compared with their natural
ligands. The calculated binding energies of their docked conformations with curcumin found to be -7.59
kcal/mol, -7.98 kcal/mol and -7.93 kcal/mol respectively. Further, a comparative study was performed to
screen binding efficiency of curcumin with two conventional antitumor agents, literol and triterpene.
Docking studies revealed that calculated binding energies of docked complex of literol and EGF, GST-PI
and PDGFA were found to be -5.08 kcal/mol, -3.69 kcal/mol and -1.86 kcal/mol respectively. The
calculated binding energies of triterpene with EGF and PDGFA were found to be - 4.02 kcal/mol and -3.11
kcal/mol respectively, whereas GST-PI showed +6.07 kcal/mol, indicate poor binding. The predicted
pharmacological features of curcumin found to be better than literol and triterpene. Our study concluded that
curcumin has better interacting properties towards these cancer targets than their normal ligands and
conventional antitumor agents. Our data pave insight for designing of curcumin as novel inhibitors against
various types of cancer.
Keywords: Curcumin, anticarcinogenic, virtual screening, epidermal growth factor, glutathione-S-
transferase Pi gene, platelet-derived growth factor, litreol, triterpene, antitumor agents














Maestro 9.4 as a tool in the structure based screening of glycoalkaloids and related compounds,
targeting Aldose reductase
M. Jannathul Firdhouse, P. Lalitha* and Shubashini K. Sripathi
Department of Chemistry, Avinashilingam Institute for Home Science and Higher Education for Women
University, Coimbatore-641043 Tamil Nadu, India
E-mail: goldenlalitha@gmail.com
Diabetes mellitus is one of the alarming common disease of this century. In India, 87 million of people are
affected by Diabetes mellitus, according to the statistics of the International Diabetes Federation and
expected to cross 100 million by 2030. This has created a thrust for the development of new medicines.
Recently, ban of pioglitazone an oral anti-diabetic drug by Drugs Technical Advisory Board (DTAB) on
account of its side effects, portrays the need for developing new drugs with less or no side effects.
Cheminformatics tools assist in screening several millions of compounds and providing lead compounds in
drug designing. Hence this paper focuses on screening of compounds for Diabetes mellitus. Aldose
reductase is a cytosolic enzyme which catalyzes the rate limiting step in polyol pathway. Hence this protein
is chosen as a receptor. Traditionally, several herbs are used in hypoglycemic control. Structure based
activity helps in arriving at lead molecules which may be anticipated to produce lowering of blood sugar.
Glycoalkaloids (present in bitter melon) and related compounds were docked onto aldose reductase and
based on the glide score, structural modifications were carried out to arrive at the highest glide score. A
commercially available molecule was also taken for reference. Glycoalkaloids were found to possess high
score compared to commercial hypoglycemic molecules. The study was conducted with two other softwares.
The flexible receptor docking of Schrodinger was found to be more advantageous than the other softwares
used. Schrodinger software can cut down millions and millions of rupees required for preliminary screening
of compounds and is a must tool for any research laboratory.

Key words: Diabetes mellitus, aldose reductase, glycoalkaloids, glide score.









Antimicrobial Activity of Cyanobacteria using In Vitro and In Silico Analysis

V. Madhumathi and S. Vijayakumar

Department of Botany and Microbiology, A.V.V.M Sri Pushpam College (Autonomous),
Poondi613 503, Thanjavur

Cyanobacteria have immense medicinal importance and are therefore used in the treatment of
bacterial and fungal organism causing oral diseases. GCMS analysis of the ethanolic extract of the
Microcystis aeruginosa and Phormidium corium has resulted in the identification bioactive compound. The
human oral cavity is a complex biological system in which members of a microbial community interact with
themselves as well as with different host structures and components of Candida albicans and Streptococcus
mutans. The pathogenesis of this dental infection is a multifactorial process that results in a serious
degenerative disease of the Oral candidiasis. In the present study SAP (Secreted Aspartyl Proteinases in
Virulence and Pathogenesis) is taken as a case study molecule to understand high reactive responses of
various drugs administered for the oral candidiasis. The drugs are being compared with the SAP from
Candida albicans and SpaP (cell surface antigen SpaP gene) from Streptococcus mutans. The SAP and SpaP
interacted with formic acid, nerolidal, octanol and nonanoic acid using docking methods.







In Silico Investigation for Interaction of Hsp90 and Its Inhibitors

Shumaila Khalid and Aparna Tewari,

National Institute of Technology Rourkela, Rourkela, Odisha

Malignant transformations like cancer and neurodegeneration disorders like Alzheimer's disease, are highly
complex processes which are generally characterized by abnormal expression, post-translational
modification, and processing of certain proteins. Currently, Cancer and Alzheimers disease (AD) are broad-
reaching and have devastating impacts on a diseased person, which needs an urgent research priority to find
various ways to manage and treat the diseases. Hsp90 is a chaperone protein which with the co-chaperones
such as p53, p23, pp5 etc assists other proteins to fold properly and helps in degradation of improperly
folded proteins. The cycle of Hsp90 occurs upon binding and hydrolysis of ATP molecules. In case of
cancer, HSP90 is overexpressed which protects the mutated oncoproteins from misfolding and proteosomal
degradation thus they are responsible for homeostatic control, stabilization, activation even in stress
conditions whereas in AD which results from the entanglement of hyperphosphorylated tau proteins, the role
of Hsp90 can either be directed towards proper refolding of tau or its proteasomal degradation.

Research
directed towards Hsp90-mediated treatment of these diseases focusses on the inhibiton of Hsp90 thereby
activating the proteasomal pathway rather than increasing the quality of the refolding process. Hence,
various drugs are now been developed which can inhibit Hsp90 by either blocking the ATP binding site
(NTD), blocking the binding site for client proteins (MD) or by blocking the dimerization site of Hsp90
(CTD). Upon in-silico investigation of various drugs under research phase common for both cancer and
AD, which are also the inhibitors of HSP90 were examined for their optimal binding energies and other
protein-ligand characteristics. The binding characteristics of all the drugs have been examined with
reference to ATP. In this work, Hsp90 alpha N-terminal domain (1YES) has been docked at ATP binding
sites like Lys 112 and Asn51 with various Hsp90 inhibitors using AUTODOCK 4 software. The efficacy of
the drugs were analyzed on the basis of binding energies and the number of hydrogen bonds. From our
experimental work it was concluded that Geldenamycin showed the lowest binding energies thus highest
binding affinity.

`

`
`




Multi- faceted utility of in silico tools to explore structure- function relationships: A case-study of
human FASN (Fatty acid synthase) multi-catalytic domain protein
Arun John
[a]
, Umashankar V.
[a]
, Deepa P. R.
[b]
, Krishnakumar S.
[c]
[a]
Dept. of Bioinformatics, Vision Research Foundation, Sankara Nethralaya, Chennai - 600006.
[b]
Dept. of Biological Sciences, BITS Pilani, Rajasthan - 333031.
[c]
Dept. of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, Chennai - 600006.
E-mail: deepa@pilani.bits-pilani.ac.in, drvus@snmail.org
In silico approaches play a key role in biological and pharmacological research. With enormous biological
data available, computational methods have become indispensable in systems biology, structural biology,
genomics and gene expression analysis
[1],[2].
As a case in point, we present our laboratory experience with
various bioinformatics tools to explore the structure function information of a multi-enzyme complex
protein, (human) fatty acid synthase (hFASN). This lipogenic enzyme is an intensively researched bio-
medical target in cancer, obesity, metabolic syndrome and infections. Still, there are several lacunae in its
structure-function understanding owing to its structural complexity and lack of complete crystal structure
information of hFASN. The crystal structure of individual domains of hFASN - MT and AT (PDB ID:
2JFK, 2JFD), KS (PDB: 3HHD) and TE (2PX6) are available. However, -hydroxy acyl dehydratase (DH),
enoyl reductase (ER) and -ketoacyl reductase (KR) domains of hFASN are yet to be elucidated
[3],[4]
.
Comparative modeling was used to predict the 3D structure of uncrystallized domains of hFASN. The
biological closeness of the predicted in silico enzyme model was examined by docking them with their
respective biochemical substrates using Glide. High throughput virtual screening was performed using
ligands (NCI Database) to identify new inhibitors for each catalytic domain (with and without crystal
structure information). These were ranked based on Glide score and optimal binding properties, for further
biochemical validation as potential pharmacologic candidates. Molecular Dynamics (MD) simulation studies
were performed to ascertain the stability of the FASN domains and structure compactness. The in silico
analyses were carried out using different applications of Schrdinger suite (Schrdinger, LLC, 2012, New
York software) and molecular dynamics using Desmond software (developed by D. E. Shaw Research, New
York). Thus, the judicious use of complementary experimental and informatics techniques enhance the hit
rate in several stages of the innovation process, from the identification of novel targets and functional
elucidation, to the discovery and development of lead compounds with desired properties, in a manner that
economizes cost and time.

References:
1.N. M. Luscombe, D. Greenbaum, M. Gerstein (2001).What is Bioinformatics? A Proposed Definition and
Overview of the Field. Method Inform Med. 40: 34658.













Docking studies of Thiazolidine derivatives using Hex and Molsoft software
Rinkesh. A. Barot
1
, Urmila H.Patel
1
, Yogesh Naliapara
2
, Chirag Bhuva
2

?
*epartment o7 Physics, Sardar Patel 0ni,ersity, )alla8h )idyanagar
2
*epartment o7 hemistry, Saurashtra 0ni,ersity, #aLkot
E-mail:- rinkesh208@gmail.com

Thiazolidine is an important kind of group in organic chemistry. Thiazolidines are five-member ring
structure having sulfur, nitrogen, and oxygen atoms and exhibiting potent as well as wide range of
pharmacological activities. Docking used for virtual screening of database and for the prediction of the
strongest binders based on various scoring functions. Protein-ligand interaction plays an important role in
structural based drugs design. In our research we have selected different receptor. The receptors are docked
with different thiazolidine derivatives and the energy value calculated. The synthesized compounds are
docked with different receptors like 1AO6, 1BUT, 1FM6, 1G2A, 1G9N, 1J4X, 1K7L, 1MWU, 1MXA,
1N2N, 1NYX, 1PRH, 1REV, 1RTD. Our study reveals that the highest energy values observed for the one
out of the several proteins which are tested, the protein 1FM6.

















COMPUTATIONAL DESIGN AND IDENTIFICATION OF A NOVEL
SQUALENE SYNTHASE INHIBITOR AS CHOLESTEROL LOWERING AGENT
A.Jerad Suresh, T.Saraswathy, K.Bhargavi*, P.Mugilarasi, K.Vimalraj

Madras Medical College, Chennai
Hyperlipidaemia, a condition characterised by elevated levels of lipids in blood, is the major cause of
cardiac illness and deaths in many people
[1,2]
. Considerable efforts have been taken around the globe, to
discover a variety of cholesterol lowering agents. Despite these efforts, for the past few decades, HMG CoA
reductase inhibitors (Statins) are widely used as hypolipidemic agents. The drawbacks of the above
including myopathy, rhabdomyolosis, hepatotoxicity etc., have led to investigation of several downstream
enzymes in the cholesterol biosynthetic pathways, as potent targets for design and discovery of New
Chemical Entities (NCE). One such target is the SQUALENE SYNTHASE that acts at the first and solely
committed step towards the synthesis of cholesterol nucleus
[3-6]
. In this study, a set of Squalene Synthase
inhibitors are chosen as ligands to generate common pharmacophoric features and quantitative models by
3D QSAR validation. The resultant models are used to screen the database molecules that are further docked
into the protein. The docked ligands are finally substantiated by running a Molecular Dynamics simulation.
REFERENCES:
[1] Rosmund, W. D.; Chambless, L. E.; Folsom, A. R.; Cooper, L. S.; ConWill, D. E.; Clegg, L.; Wang, C.
H.;Heiss, G. N. Eng. J. Med. 1998, 339, 861.
[2] Murray, C. J. L.; Lopez, A. D. Lancet 1997, 349,1269.
[3] Harwood, H. J., Jr., Barbacci-Tobin, E. G., Petras, S. F., Lindsey, S., and Pellarin,L. D. (1997)
Biochemical Pharmacology 53(6), 839-64

[4] Lindsey, S.,and Harwood, H. J., Jr. (1995) Journal of Biological Chemistry 270(16), 9083-96

[5] Bergstrom, J. D., Dufresne, C., Bills, G. F., Nallin-Omstead, M., and Byrne, K. (1995) Annual Review
of Microbiology 49, 607-39

[6] Biller, S. A., Neuenschwander, K., Ponpipom, M. M., and Poulter, C. D. (1996) Curr. Pharm. Des. 2(1),
1-40









In-silico Docking and Molecular Dynamics Simulation of Some Pyrazolo[3,4-d]pyrimidine derivatives
as antiamoebic agents

Umesh Yadava
1
*, Bindesh Kumar Shukla
1
and Devesh Kumar
2
1
Department of Physics, D.D.U. Gorakhpur University, Gorakhpur- 273009
2
Department of Applied Physics, B.B.A. Central University, Lucknow- 226001

Amoebiasis is a common infection caused by a protozoan parasite, Entamoeba histolytica that infects the
large intestines of humans and in advance stage liver, brain and lung. It can cause abcesses and ulcers and
may infect the bowel. If not treated, it can be highly fatal to a person. Metronidazole, the first line
medicament against amoebiasis, is potentially carcinogenic to humans because it is genotoxic to human cells
and a shows significant side-effects. The in-vitro studies divulge that pyrazolo[3,4-d]pyrimidines may have
better inhibitor activity in comparison to metranidazole. In present work, the in-silico molecular docking
simulation of nine pyrazolo[3,4-d]pyrimidine molecules having no linker, nine pyrazolo[3,4-d]pyrimidine
molecules having trimethylene linker and the reference drug metranidazole have been performed with O-
acetyl-L-serine sulfhydrylase enzyme, the prime target for inhibiting the growth of E.Histolytica. Molecules
2 and 4 of the molecules without linker have been proven to be the better inhibitors than metranidazole.
Trimethylene linker molecules show better binding capabilities among which molecules 15 and 16
supersede. Molecular dynamics simulation on the best docked poses of molecules 2, 4, 15, 16 and MNZ
have carried out for 10ns using DESMOND. MD results demonstrate that the complexes remain stable
during the course of dynamics. Thus pyrazolo[3,4-d]pyrimidie analogues will be helpful in developing new
drugs against antiamoebic histolytica disease with high antiamoebic activity.














NATURAL FLAVANOIDS AS POTENTIAL ALDOSE REDUCTASE INHIBITORS: A
MOLECULAR MODELLING STUDY
R. Krishna Chaitanya, M. Rupa, R. Sunil Kumar, Naresh Panigrahi, V. Suresh Babu, Padilam Suresh
GITAM Institute of Pharmacy, GITAM University, Rushikonda, Visakhapatnam.-530045

Aldose reductase inhibitors (ARIs) inhibit the first step of hyperglycemia-induced polyol pathway and these
inhibitors act as potential therapeutic candidates in the treatment and prevention of diabetic complications.
Flavonoids are natural substances with variable polyphenolic structures which are widely distributed
throughout the plant kingdom and exhibit several biological activities including aldose reductase inhibition.
The primary goal of this study was to investigate the detail interactions of some selected therapeutically
useful flavonoids in the core pocket of aldose reductase enzyme using in silico docking studies. In silico
docking studies were carried out using Glide powerful molecular modeling software. In the present study 50
natural flavonoids having potential aldose reductase inhibition were docked (XP mode) in the binding
pockets of respective enzyme with PDB ID 1US0 co-complexed with inhibitor IDD594 at 0.66 angstrom
resolution. The root mean square deviations (RMSD) between the predicted conformation and the observed
X-ray crystallographic conformation of compound IDD594 equaled 0.7 by Glide indicates the reliability
of the docking method. From the docking studies flavonoids like Desmanthin-1, Quercitrin, Guaijaverin-4,
Luteolin, and (2S)-Eriodictyol 7-O-GlcA have shown the highest XP docking scores which are further
correlated with their pIC50 values. A correlation coefficient of R = 0.7413 between experimental pIC50 and
XP docking scores was obtained using Glide. Investigation of the docking studies shows most of the
flavonoids have stacking with TRP-111 residue and the phenolic hydroxy groups at 3,7 positions
enhances the inhibitory activity.















SHAPE-BASED DOCKING ANALYSIS OF PHOSPHORYLATED INSULIN KINASE RECEPTOR
TYROSINE KINASE WITH MUSA SAPEINTUM FLOWER ALKALOIDS AND FLAVONOIDS
Das Souvik Prasanta
1
, Dr. Sushil Kumar Midha
2
Department of Bioinformatics, SRM University
1
, Chennai,
Bioinformatics Department (DBT-BIF) Maharani Lakshmi Ammani College for Women, Bangalore
2

Diabetes mellitus is an independent risk factor for the development of coronary artery diseases, myocardial
infarction, hypertension, and dyslipidemia. Clinically diabetic patients are characterized by marked increase
in blood glucose level followed by mild hyperlipidemia. Non-insulin dependent diabetes mellitus (NIDDM)
accounts for approximately 8090% of all cases and it is the fastest growing global threat to public health.
Insulin receptor is a tetramer that belongs to a family of receptor tyrosine kinases. It contains two alpha
subunits that form the extracellular domain and two beta subunits that constitute the intracellular tyrosine
kinase domain. Insulin binds to the extracellular region of the receptor and causes conformational changes
that lead to the activation of the tyrosine kinase. This leads to autophosphorylation, a step that is crucial in
insulin signaling pathway. Hence, compounds that augment insulin receptor tyrosine kinase activity would
be useful in the treatment of diabetes mellitus. Musa Speintum flower is a rich source of such compounds.
The flower consists of alkaloids and flavonoids that exhibit anti-diabetic and anti-hyperglycemic activity.
The 3-dimensional structure of the Insulin Receptor tyrosine kinase was obtained from PDB. The list of
alkaloids and flavonoids found in Musa Sapeintum flower was obtained from Dukes and USDA database
respectively. The structures of the respective anti-oxidants were obtained from Drugbank and NCBI
Pubchem and drawn using Marvin Sketch. Our work involves the inhibition study of this target with 25 anti-
hyperglycemic natural compounds using AutoDock 4.0. The best docking poses have been elucidated which
in turn be a probable lead against this target.
Key-words:- Diabetes Mellitus, NIDDM, Musa Sapeintum, Flavonoids, Alkaloids, Anti-hyperglycemic
activity, Docking.











Probing the binding of Syzygium derived -glucosidase inhibitors with N and C terminal Human
Maltase Glucoamylase by docking and molecular dynamics simulation
Debasish Roy
1
, Vinod Kumar
1
, Joel James
1
, Kshitish K Acharya
2
and Kavitha Thirumurugan
1
*
1. 206, Structural Biology Lab, Centre for Biomedical Research, VIT University, Vellore- 632014,
Tamil Nadu, India.
2. Shodhaka Life Sciences Pvt. Ltd, IBAB Biotech Park, Electronic City, Phase 1, Bengalooru
560100, Karnataka, India
E-mail: m.kavitha@vit.ac.in

Human Maltase Glucoamylase (MGAM) is a potent molecular target for controlling post prandial glucose
surplus in Type 2 Diabetes. Binding of small molecules from Syzygium sp. with -glucosidase inhibitory
potential in MGAM has been investigated in silico. Our results suggest that Myricetin was the most potent
inhibitor with high binding affinity for both N and C terminals of MGAM. Molecular Dynamics revealed
that Myricetin interacts in its stretched conformation through water mediated interactions with C terminal of
MGAM and by normal hydrogen bonding with the N terminal. W1369 of the extended 21 amino acid
residue helical loop of C terminal plays a major role in Myricetin binding. Owing to its additional sugar
sites, overall binding of small molecules favours C terminal MGAM.


















Chemosensitizing acridones: In vitro calmodulin dependent cAMP phosphodiesterase inhibition,
docking, pharmacophore modeling and 3D QSAR studies

Deepak Reddy Gade
1,2
*, V.V.S. Rajendra Prasad
1
1
Medicinal Chemistry Research Division, Vishnu Institute of Pharmaceutical Education and Research,
Narsapur, Medak Dist. AP., India.,

2
Faculty of Pharmaceutical Sciences, Jawaharlal Nehru Technological University, Hyderabad, AP. India.
E-Mail: deepakreddy.g@viper.ac.in, deepakr47@gmail.com

Drug resistance is a phenomenon that frequently impairs proper treatment of infections and cancer
with chemotherapics. Multidrug resistance (MDR) is a case of acquired resistance of cancer cells to multiple
classes of chemotherapeutic drugs that can be structurally and mechanistically unrelated. Cells exhibiting
MDR accumulate a lower intracellular concentration of drug. This effect is associated with accelerated
efflux of antitumour agents by an ATP-dependent process. Along with genetic mutations of the cellular
structures and detoxifying systems, drug resistance occurs through expression of some special ATP-
dependent pumps such as P-glycoprotein and Multidrug resistant associated proteins (MRPs) which pumps
out the cytotoxic chemicals from the cell for its survival. These efflux pumps belong to the ATP binding
cassette (ABC) transporters family sharing sequence and structural similarity. Most common
chemotherapeutic agents that are effluxed by these proteins are doxorubicin, daunorubicin, vincristine,
vinblastine and taxols. Calmodulin inhibitors have proved to play a significant role in sensitizing MDR
cancer cells by interfering with cellular drug accumulation.
In the present study we have identified an efficient pharmacophore from a set of 38 N
10
-substituted
acridones which reverts doxorubicin resistance in HL-60 cell line. Identified pharmacophoric features such
as one hydrogen bond acceptor, one hydrophobic region, a positive ion group and three aromatic rings i.e,
AHPRRR. Ligand based 3D-QSAR was performed by employing Partial Least Square regression analysis
which gave a regression coefficient R
2
of 0.98 and Q
2
of 0.86, and Pearson-R of 0.95. Another
pharmacophore model of same compounds with same set of pharmacophoric features with different 3D
spatial arrangement showed that 0.95 (R
2
), 0.87(Q
2
) and 0.94 (Pearson-R). Molecular docking study was
performed for cholro acridones against calmodulin dependent cAMP phosphodiesterase enzyme (PDE1c) in
order to identify the possible protein ligand binding interactions and results thus obtained were compared
with in-vitro data, good correlations were found between in-silico and in-vitro results.








Designing of Selective TACE Inhibitors: Application of Induced Fit Docking and Analysis of Active
Site By Using Molecular Docking For Defining the Selectivity of TACE Over MMPs

Ajinkya P. Sarkate
a
, Prashant R. Murumkar
a
*, Deepak K. Lokwani
b
, Devanand B. Shinde
b
and
Kailash G. Bothara
a
, ajinkyasarkate@gmail.com

a
Department of Pharmaceutical Chemistry, Sinhgad Institute of Pharmacy, Narhe, Pune-411041,
Maharashtra, India
b
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad-
431004, Maharashtra, India
E-Mail: prashant_murumkar@yahoo.com

TNF- converting enzyme (TACE) has been considered as one of the principal therapeutic target for the
treatment of TNF-dependent pathologies. Till date several TACE inhibitors have been reported, but none of
them have been passed successfully Phase II clinical trials. In present work, we attempted to design highly
selective new sulfonamide non-hydroxamate TACE inhibitors. The designed compounds were docked on
different crystal structures of TACE for analyzing the binding mode/score. Further, the flexible induced fit
docking study of designed compounds was performed to compare the change in docking pose/score and the
binding affinities of compounds toward TACE. The results allowed us to identify the analogues bearing
amino acids with long aliphatic or aromatic side chain at zinc binding site of inhibitors, with more binding
affinity toward TACE. Finally the analogues were docked on crystal structures of six different matrix
metalloproteinases (MMPs) for selectivity study of TACE over MMPs.
Keywords: TACE, Sulfonamide, Glide, Induced fit docking (IFD), MMPs








MOLECULAR MODELLING AND DOCKING ANALYSIS ON SHRIMP VITELLOGENIN
RECEPTOR AND LIGAND TARGET MEDIATED DELIVERY SYSTEM

S. DIVYA PRIYA,

BHARATHIDASAN INSTITUTE OF TECHNOLOGY, ANNA UNIVERSITY, TRICHY.

EMAIL: divyapriya67ph@gmail.com



Viral pathogens of shrimp such as the white spot syndrome virus (WSSV), Yellow head virus (YHV), Taura
syndrome virus (TSV), Hepatopancreatic parvovirus (HPV), and Monodon Baculovirus (MBV), which are
geographically widespread, are major concern in shrimp aquaculture due to the associated huge economic
loss . The control of such diseases is a challenging task for the shrimp aquaculture industry. Drug delivery
mediated by specific receptor and ligand interaction plays an important role in effective control of diseases.
In the present study focus on vitellogenin receptor and ligand interaction for targeted drug delivery for
control of MBV infection in black tiger shrimp (Penaeus monodon) was explored by insilico studies.
Vitellogenin protein receptor of shrimp P. monodon and ligand molecules sequences were retrieved from
public domain. Molecular modeling and docking studies were explored by using online bioinformatics tools.
The results suggested that 20-hydroxy ecdysone might be a potential target of vitellogenin receptor for
effective targeted drug delivery system for control of monodon baculovirus.

Key words: Monodon bavulovirus, Black Tiger Shrimp, Vitellogenin, 20-hydroxyecdysone, Molecular
modeling and docking.















DOCKING STUDIES OF SOME NEW THIAZOLIDINONE DERIVATIVES AS ANTICANCER
AGENT WITH RECEPTOR PROTEIN KINASE INHIBITORS

Pragya Nayak, Monica Kachroo

Al-ameen College of Pharmacy, Bangalore


A series of thiazolidin-4-one derivatives containing thiadiazole moiety were designed and their docking
studies were performed to determine their potential as receptor protein kinase inhibitors and also their
anticancer potential based on the reviews of the literature reporting the potential of thiazolidinone
derivatives as EGFR and HER-2 inhibitors. Their receptor binding affinities and binding patterns were
studied to identify the possible modifications in the molecule to develop the probable binding model with
better anticancer activity.
Keywords: Thiazolidinone, Thiadiazole, Protein kinase inhibitors.



















DOCKING STUDY OF INDOLE DERIVATIVES AS FLAP ENDONUCLEASE INHIBITOR
Pankaj Wadhwa, Priti Jain, Hemant R Jadhav
Department of Pharmacy, BITS Pilani, Pilani Campus, Jhunjhunu, Rajasthan-333031
E-Mail: pankajwadhwa88@gmail.com

Flap endonucleases (FENs) play key role in cells by taking part in DNA replication and long-patch base
excision repair (LP-BER). Base excision repair (BER) pathway is one of the most important pathways for
repairing the damaged DNA. Overexpression of FEN is causative reason behind various types of cancers.
Hence, inhibition of this enzyme may lead to effective anticancer therapy. Novel Indole derivatives were
docked on FEN protein (PDB: 1UL1). The results reveal strong electrostatic and hydrogen bonding
interactions with active site of flap endonuclease enzyme i.e. Asp 86, Asp 179, Asp 181, and Asp 233. They
are also found to inhibit its activity by binding with Mg ions by forming the covalent bond. Development of
these novel indole derivatives may enhance potential of chemotherapeutic agents by synergistic action. The
docking process adopted and results obtained will be discussed.



















In-vitro cyclo-oxygenase inhibitory effect of plant extracts and their fractions
Dushyant Kumar
1
, HV Hegde
1
, S G Alegaon
3
, S Roy
1
, S D Kholkute
1


1. Regional Medical Research Centre (ICMR), Nehru nagar, Belgaum, Karnataka, India 590010.
2. KLE University College of Pharmacy, Belgaum, Karnataka 590010


Inflammation is a common clinical condition for daily clinical practice. Available anti-inflammatory agents
are not safe for long term use and most of them share common adverse effect like, gastric ulcer,
cardiotoxicity etc. Several herbal formulations are used frequently in the traditional medical system to treat
joint pain, which are believed to be effective and have lesser side effects. Hence, two plant viz: Plumbago
zeylanica Linn. root and Holoptelea integrifolia Roxb. bark extracts and fraction of active extract were
selected to screen anti-inflammatory effect using cyclo-oxygenase inhibitory in-vitro model. The
assessments were made to quantify prostaglandins after incubation with extracts and fractions. Reported
chemical constituents of the plants were subjected for docking study against active site of cyclo-oxygenase
inhibitor (COX II) 1CX2 PDB file with Mastero 9.4 (SCHRDINGER). The results were expressed as
percentage inhibition on cyclo-oxygenase I and II respectively with IC50 value. Maximum reduction was
observed in hydroalcoholic extracts and fraction # 3 from both the plants. Plumbagic acid and plumbagin
docking score were -9.566 and -7.857 respectively. The study supports the utility of these plants in the
treatment of pain and inflammation. Further studies are in progress to find out their active ingredient(s) and
their mechanism of action.












G2PU Accelerated Automated Docking Software With Integrated Plant Chemical DB
as Repository of Ligands: An Ayurinformatics Approach

Subrata Sinha*, Deep Jyoti Das, Hemchandra Deka, Vishal Paul and Rashmi Jha, Rabika S. Khati
Center for Bioinformatics Studies, Dibrugarh University, Dibrugarh-786004, Assam.
E-Mail: subratasinha@dibru.ac.in


In the era of modern drug discovery the chemical compounds of medicinal plants, played a major role as a template
for synthesis of new drugs, but only 10-15% of plant chemicals has been so far explored, and so In Silico drug
discovery industries needs to conduct a massive level study on protein-ligands interactions with phytochemical as
potent ligands .The major challenges faced by the industries are the time consuming unreliable phytochemical
screening and docking methods. So, in this paper an attempt has been made to propose a architectural schema of a
G2PU Accelerated Automated Docking Software with builtin phytochemical database, target protein database
powered by ancient knowledgebase of Ayurveda . The docking is performed between target proteins and
phytochemical in two approaches - brute force method and ancient knowledge based method in which the docking is
performed with phytochemical of those plants mentioned in the ancient scriptures of Ayurveda as remedy of diseases.
The computational load is shared proportionately between CPU and GPU. The experiment was performed on Intel HD
4000 Integrated Graphics Processor with 16 EU operating at 1350 MHz on Open CL Platform.

Keywords: Automated docking, G2PU, Ayurinformatics, Heterogeneous Computing.













Structure-based virtual screening and evolutionary analysis for the identification of
small molecule inhibitors to abrogate protein-protein interactions and paracrine
Hedgehog Signaling

A. Gandhimathi and R. Sowdhamini
National Centre for Biological Sciences, Tata Institute of Fundamental Research
GKVK Campus, Bellary Road, Bangalore-560065

Hedgehog (Hh) proteins are important secreted signaling molecules, critical for tissue
patterning events during embryonic development and tissue homeostasis and regeneration.
The nanoscale organization of Hh oligomers has opened up new ventures for designing
small molecule inhibitors that could disrupt Hh oligomer formation or impair paracrine
signalling in abnormal conditions. We have performed virtual screening, starting from a
set of 1,70,000 small drug-like molecules, against Drosophila Hh protein and obtained
~800 molecules. Further, these molecules were clustered into mere 107 types based on
ligand scaffold similarity. Subsequently, induced fit docking method was performed on
each cluster centre, whereby a novel series of potent leads have been suggested based
on the interactions with Drosophila and Human Shh. Further, evolutionary trace analysis
was performed to analyse the conserved and class-specific residues between vertebrate
and invertebrate Hh proteins. The results are consistent with the earlier findings that
vertebrate and invertebrate Hh interactions with co-receptors are not conserved. The
information on residue conservation would eventually help to identify potent inhibitors
for Hh-receptor interactions as well.



























PREDICTION OF INTERACTION BETWEEN -GLUCOSIDASE WITH GANODEROL-B AND
ACARBOSE: AN IN-SILICO APPROACH

T.Mowna Sundari and R.Shenbagarathai

Approximately 347 million people across the world have been affected with diabetes mellitus (DM) as per
WHO report. It is estimated that diabetes will be the 7
th
leading cause of death by the year 2030. There are
several types of DM including type I, type II and gestational, among which type II is predominant with 90%
occurrence. Type II DM normally referred as non-insulin dependent diabetes mellitus or adult onset diabetes
occurs when the cells fail to utilize insulin. The enzyme -glucosidase is considered as a potent target to
treat type II DM. Hence, commercially available drugs have been designed to inhibit the action of -
glucosidase (Acarbose, Glibenclamide, Metformin, Pioglitazone, Nateglinide and Glybuzole). But these
drugs were known cause drug resistance on prolonged usage. So there is a great need for more efficient -
glucosidase inhibitors that could reduce the risk of diabetes related complications. Ganoderol-B, a
triterpenoid from Ganoderma lucidum has recently been reported as potent
-Glucosidase inhibitor far superior than the standard drug, Acarbose. Hence, the present study focused on
the elucidation of potential binding of ganoderol-B with -glucosidase (PDB id: 3VKK). The ligands were
prepared using LigPrep tool and its properties were analysed by QikProp tool. Molecular docking was
performed using GLIDE Tool (Schrodinger Maestro). It was observed that the interaction between
ganoderol-B and -glucosidase (Glide score: - 6.773) was very efficient in comparison to Acarbose and -
glucosidase (Glide score: - 5.612). Ganoderol-B warrants good potential candidate for development of anti-
diabetic drug. Further in vivo toxicity studies are required to evaluate its safety margin.

Keywords: Diabetes mellitus; -glucosidase; Ganoderol-B; Acarbose; Docking




Employing remote homology detection tools to re-purpose drugs: A case study with
Mycobacterium tuberculosis H37Rv

Gayatri Ramakrishnan
1
, Nagasuma R. Chandra
2
and Narayanaswamy Srinivasan
3

1
Indian Institute of Science Mathematics Initiative,
2
Department of Biochemistry,
3
Molecular Biophysics
Unit, Indian Institute of Science, Bangalore-560012, Karnataka, India

Drug re-purposing or drug re-profiling to explore target space has been gaining pace over the past decade.
Novel technological initiatives, such as high-throughput screening, structure-based drug design and
combinatorial chemistry, have yielded fewer successful results against the cost and time invested, thus
forcing biopharmaceutical companies to leverage investments on a more promising strategy- to re-purpose
known drugs. Owing to global burden of tuberculosis and the emergence of totally drug-resistant strains of
the pathogen, evolutionary relationships between targets of known FDA-approved drugs and the protein
repertoire of Mycobacterium tuberculosis H37Rv (Mtb) have been explored in order to recognize putative
drug targets in the pathogen. To make the most of sequence and structural data, a combination of multiple
approaches for remote homology detection facilitated identification of unexploited Mtb proteins that could
serve as attractive targets. To minimize the chances of obtaining an anti-target, the FDA-approved drugs
were initially subjected to a filter, where the drugs known to act on human proteins were discarded. In
retrospect, a total of 132 FDA-approved drugs were identified which could be repositioned for 190 potential
targets in Mtb. A comprehensive drug-target network aided recognition of 66 drugs which could potentially
act on multiple targets (polypharmacological drugs) and 80 targets on which a combination of multiple
drugs could potentially be used. A very efficient protein-ligand docking tool, Glide (Schrodinger suite), has
been of an immense aid in assessing the credibility of the predictions made.
An imperative step towards perceiving the biology of a pathogen is to comprehend the functional repertoire
encoded in its genome which in turn, facilitates understanding the inherent complexities in host-pathogen
interactions. Curtailing the incompleteness in previously annotated genome, we report an enhanced
structural and functional characterization of ~93% Mtb proteins, with the help of combination of sensitive
profile-based remote homology approaches. This information served as a guiding tool in analyzing
functional importance of attractive targets identified and thus these targets could be prioritized for future
experimental endeavors.








In silico drug Docking of phyto inhibitors for Human Placental Aromatase

Geetanjali Thorat

Department of Bioinformatics, G. N. Khalsa College, Matunga, Mumbai, India

E-mail: geetnjalithorat45@yahoo.com

Aromatase inhibitors are effective form of endocrine therapy as a treatment for hormone sensitive breast
cancer. Worldwide breast cancer estimated included over one million incident cases and almost 400,000
deaths in the year 2000. Numerous molecular targets have been identified as playing a significant role in
breast cancer development and progression. Estrogens and the estrogen receptor (ERs)

are widely
recognized to play an important role in the development and progression of breast cancer, making estrogens
and ERs widely studied molecular targets. Two of the endogenous estrogens found in humans include
estradiol and estrone. In pre- menopausal women, estrogens are produced primarily through conversion of
androgens in the ovaries while estrogen production in post-menopausal women occurs in only peripheral
tissues. Aromatase is a cytochrome p450 enzyme and is responsible for catalyzing the biosynthesis of
estrogens (estrone and estradiol) from androgens (androstenedion and testosterone). The concentration of
estrogens has been shown to be as much as twenty fold higher in breast cancer tissues than in the
circulating plasma, suggesting locally increased aromatase expression for estrogen biosynthesis near or
within the cancerous tissues. An attempt was made to identify the potential phyto inhibitor with its structural
analogous and inhibit the enzyme as well as to modify their side chain to impure the binding efficiently.
Here, potential molecules were screened out using 3D QSAR by dividing the data into two datasets as
training set and testing set whose model was used to predict 150 phyto inhibitors to be tested. The top
promising molecules were docked for the binding pose by Induce fit docking for accurate ligand induced
conformational changes in receptor active sites. I have shown that experimentally determined binding
operations and computed energies of known ligands can be reproduced accurately for future experiments.

Key words: Binding, Docking, Aromatase inhibitor, Hormone sensitive breast cancer.
References:
[1]. Ferlay, J.; Bray, F.; Pisani, P.; Parkin, DM. GLOBOCAN 2000: Cancer Incidence, Mortality and
Prevalence Worldwide, IARC Cancer Base No. 5. International Agency for Research on Cancer (IARC)
Press; Lyon: 2001.












INSILICO ANALYSIS OF ALGAL TOXIN INTERACTION WITH PROTEIN PHOSPHATASE
S.Gopinath
1
L.A.Shivaram
2
Mrs. Shobana*

Microcystin, a class of hepatotoxins produced by species of freshwater cyanobacteria primarily Microcystic
aeruginosa. These are cyclic nonribosomal peptide toxins, which are found, related to the incidents of
human illness and animal poisoning. In addition to their acute hepatotoxic effects, they have also been found
to act as tumor promoters. Microcystin-LR (L and R identifying the 2 variable amino acids, in this case
leucine and arginine respectively). It consists of several uncommon non-proteinogenic amino acids such as
dehydroalanine derivatives and the special -amino acid ADDA (3-Amino-9-methoxy-2, 6, 8-trimethyl-10-
phenyldeca-4, 6-diene acid). The ADDA moiety is responsible for its toxicity. The main aim is to study the
interaction of Human Protein phosphatase and microcystin and to find a better potential inhibitor against
microcystin by means of ligand based pharmacophore studies using the known ligands. Insilico analysis was
performed using Schrodinger 9.1.

Keywords: %icrocystin, hepatotoxin, docking.





















-nderstanding amantadine drug resistance and Identification of common in(i)itors for wild-type and './
mutant of M0 proton c(annel

Krishnasamy Gopinath and Muthusamy Karthikeyan *
*epartment o7 Bioin7ormatics, Science Block, "lagappa 0ni,ersity, (araikudi G M'0 004, ;amil $adu, .ndia.
*Mail: mkbioinformatics@gmail.com
;he in7luen2a " %2 channel protein is crucial 7or ,iral replication. .t has 8een considered as maLor target 7or
in7luen2a in7ection. "mantadine 5"%"6 and #imantadine 5#.%6 are t9o drugs 9idely used to control the in7luen2a
,irus 8y inhi8iting %2 proton channel. .t 9as reported that single site mutation o7 %2 proton channel caused
resistance o7 in7luen2a ,irus to these "mantadine 5"%"6 and #imantadine 5#.%6 drugs. .n the present study, 9e
conducted a systematic in si(ico approach to explore the structural 8asis underlying this drug resistance mechanism.
By molecular docking analyses and molecular dynamics 5%*6 simulations, 9e compared 9ild type and S'?$ %2
proton channel 9ith "%". ;he docking score and 8inding energy o7 "%" 9ith S'?$ 9as su8stantially lo9er than
9ild type protein. Further, /igh throughput ,irtual screening 5Binding data8ase6 9as employed to screen the
potential inhi8itor 7or 8oth I; and S'?$ mutated %2 proton channel. ;hree compounds 5Binding*BN?&?&0,
Binding*BN?O?O&, Binding*BNP'OC6 9ere selected 8ased on docking score, 8inding energy and "*%E properties.
Further, %* simulations 9ere carried out to compare the sta8ility o7 ligands in 8oth 9ild and mutant proteins. ;he
result sho9s that all the three compounds ha,e higher sta8ility than "%". ;hese 7indings expected to pro,ide
signi7icant insights into impro,ing inhi8itors o7 drug resistant %2 protein o7 in7luen2a ,iruses.
(ey9ords : "mantadine, ommon inhi8itors, *rug resistance, %23S'?$ mutation
1cknowledgments:;his 9ork 9as 7ully supported 8y the ouncil o7 Scienti7ic and .ndustrial #esearch 5S.#6 grant,
@o,ernment o7 .ndia 5@>.6, $e9 *elhi. "uthors thank7ully ackno9ledge the S.#, $e9 *elhi 7or the 7inancial support
rendered to (@ through Senior #esearch Fello9ship.










In Silico Docking approach to elucidate the inhibitory effect of thiazides on Aspartic
Acid Proteases
Agarwal T., Gupta P., Asthana S., Vajanthri K.Y., Banerjee I.*
Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha
Email: indraniliit@gmail.com

Aspartic acid proteases are amongst the important class of proteases which are regarded crucial for
pathogenesis of few important pathogens. Inhibition of these proteases can play an important role in
tackling these diseases. HIV-1 protease and Plasmepsins present in HIV and Plasmodium species
(Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae respecti!ely" are critical
en#ymes for the life cycle of these organisms. $he ma%or problem which has come into e&istence
recently is the gain of resistance by these organisms for currently a!ailable therapeutics. 'o" there is
an urge to de!elop new drugs to handle the drug resistant !ersion of these organisms. In the present
study" we in!estigated thia#ides and its deri!ati!es for their bioaffinity towards Plasmepsins and HIV-
1-protease by implying molecular docking approach using (amarckian )enetic Algorithm using
Autodock*.+. $he metabolite structure was retrie!ed from ,-Ap'Ac,-./ database. $he grid maps
representing the protein were calculated using auto grid and grid si#e was set to 01201201 points
with grid spacing of 1..34 5. /ocking was carried out with standard docking protocol on the basis of a
population si#e of 141 randomly placed indi!iduals6 a ma&imum number of +.4 211
3
energy
e!aluations" a mutation rate of 1.1+" a crosso!er rate of 1.71. $en independent docking runs were
carried out for each ligand and results were clustered according to the 1.1 5 rmsd criteria. Hydrogen
bond analysis was done by 89': 9himera. ;olecular" A/;< (Absorption" /istribution" ;etabolism
and <&cretion and to&icity properties calculation were carried out using PreA/;<$ ser!er. $he
results demonstrated that the binding energies against Plasmepsin II protein model 1';< and HIV-1-
protease protein model 1A=V were -1+.10kcal>mol (9I/?3104+ and -11.+1kcal>mol (9I/?+.413+3
respecti!ely. $he ligands e&hibited good drug-likeness score" encompassed good A/;< properties
and showed no carcinogenicity and to&icity. :urther in-!itro and in-!i!o study is re@uired for the
future design of new deri!ati!es with higher potency and specificity.
Keywords: Plasmepsin" HIV-1-protease" $hia#ide" Aspartic protease inhibitor" Autodock *.+









Unraveling odor receptor- odor interaction patterns
K.Harini and R.Sowdhamini
National Centre for Biological Sciences (TIFR), GKVK, and Bellary Road, Bangalore 65


All living organisms are able to detect and discriminate countless
structurally diverse odorants. This sensory function is mediated by
olfactory receptors (ORs) found in the plasma membrane of the olfactory
receptor neurons present at the olfactory epithelium. Each neuron
expresses only one of the thousand different olfactory receptor at a time
(Lewcock J.W 2004, Serizawa S 2003). Mammalian olfactory receptors belong
to class A type G-protein coupled receptors (GPCRs) (Buck and Axel 1999).
The olfactory receptors form a multigene family consisting of over 900
genes in humans and 1500 genes in mice. Unlike GPCRs olfactory receptors
exhibit a combinatorial response to odors. Rather than binding specific
ligands, olfactory receptors display affinity for a range of odor
molecules, and conversely a single odorant molecule may bind to a number
of olfactory receptors with varying affinities. This mechanism which is
poorly understood gives the olfactory receptors the power to discriminate
between countless odors. The diversity and variability in detecting odors
has been associated with highly variable transmembrane domain of these
receptors. In Silico analysis of amino acid variablity among about 200
ORs has shown that most of the highly variable residues are present in
transmembrane domains 3,4 and 5 (Pilpel.Y 1999). Adipietro KA (2012) et
al have shown that OR orthologs are similarly tuned within an OR set, but
that dramatic differences in efficacy and potency to a common odor are
frequent. Several studies have been done in past to analyze ligand binding
site of olfactory receptor using several different approaches. Here, we use
homology modeling and docking studies to compare ligand binding residues
between human and mouse OR orthologs. We show that orthologous olfactory
receptor sequences do not recognize common ligand but their ligand binding pocket
superpose well at the structural level most of the times.









In-silico stabilization of Microtubule by Taxane Diterpenoids

Umesh Yadava*, Ramesh Kumar Yadav and Hari Om Gupta
Department of Physics, DDU Gorakhpur University, Gorakhpur-273009 India
Email: u_yadava@yahoo.com

Microtubules are formed from the molecules of tubulin, whose dynamics is impartment of many
functions in cell, the most dramatic of which is mitosis. Taxol is known to interact within a specific site on
tubulin. Taxol is believed to block cell-cycle progression during mitosis by binding to and stabilizing
microtubules. Along with the tremendous potential that taxol has shown as an anticancer drug, clinical
problem exist with solubility, toxicity and development of drug resistance. The crystal structure of taxane
diterpenoids namely, 10,13-deacetyl-abeo-baccatin-IV (I) and 5-acetyl-2-deacetoxydecinnamoyl-
taxinine-0.29hydrate (II), 7,9-dideacetyltaxayuntin (III) and Taxawallin-K (IV) are very similar to the
taxol molecule. These molecules are supposed to be the alternative of Taxol with less side effects. These
molecules form cage like conformations which is found to be necessary for binding to tubulin.

In the present
work, the Molecular docking of these taxane diterpenoids have been carried out with the tubulin alpha-beta
dimer (1TUB) and refined structure of microtubule (JFF) in order to assess the potential of tubulin binding
of these cytotoxic agents. The Glide module of the Schrodinger suite has been used for molecular docking.
Results reveal that molecules I - IV dock into the taxol binding site of tubulin with comparable docking
energies to taxol. The docking energy, glide score and hydrogen bonding interactions show that compound I
has better tendency of binding with bovine tubulin(1JFF), while II has better binding capability with 1TUB
than other diterpenoids.














Molecular modeling of Calcineurin A and prediction of high affinity binding peptide fragments
derived from Auto Inhibitory Domain by Schrdinger software
Harish B.M, Saraswathi R, Gopi A, Anushree and Devaraju K.S
Department of Microbiology and Biotechnology, Jnana Bharathi Campus, Bangalore University,
Bangalore-560 056
Email:ksdevaraju@bub.ernet.in/devarajuks@gmail.com

Calcineurin (CN) is usually targeted to inhibit its function during organ transplantation by using
Cyclosporine (CsA) and FK506 to suppress immunity. CN activity could also be inhibited by auto
inhibitory domain (AID) which is present in C-terminal of CN A chain. However, this binding domain and
its fragments were not been studied for their inhibitory properties. Hence, the binding affinity studies of
docking complex by in silico approaches was done and also because of non availability of complete
structure of CN in PDB, we have modeled CN A containing auto inhibitory domain by using Prime
(Version 11, Schrdinger, LLC). The modeled CN A has been used to generate 275 peptide fragments from
its auto inhibitory domain. Further these fragments were docked by using Glide (Version 11, Schrdinger,
LLC). The docking energy of all the fragments with CN A chain were analyzed and compared with AID.
Docking results shows peptide fragment range 473-483 has highest binding affinity than AID. Further
Molecular dynamic simulation using Desmond (Version 11, Schrdinger, LLC) suggest that predicted
peptide 473-483 has more stability at active site than AID. Hence, our study concludes that 473-483
fragment can be used as a potent inhibitor of CN.












Ganoderic Acids: potential leads for Cancer
Pilley H. H. and Wadegaonkar P. A
Bioinformatics Infrastructure Facility (BIF), Department of Biotechnology, Sant Gadge Baba
Amravati University, Amravati, Maharashtra, India 444602

Ganoderma lucidum (Ling-Zhi or Reishi) is one of the sources for most productive and
pharmacologically active compounds found in Asian countries. Its active ingredients mainly include
terpenoids, polysaccharides, sterols, steroids, proteins etc. Out of these metabolites, terpenoids mainly
ganoderic acids contribute a lot for its anticancerous behavior. This study aimed to elucidate
interactions for one of the active compounds of Ganoderma lucidum namely ganoderic acids with NF-
B using molecular docking. Among major regulators of tumor survival, proliferation, invasion,
angiogenesis, metastasis; the nuclear factor-kappaB (NF-B) activation contributes to the
development tumor cells which leads to cancer. The Molecular properties, Lipinski properties and
ADMET properties of the active ganoderic acids were calculated. Prepared ligands and target protein
were docked with different conformation with predicted active site using Schrdinger Maestro 9.4
software modules. These observed interactions not only suggested NF-B in general is a suitable
target for ganoderic acids, they also indicated a huge potential for cancer drug discovery based on this
compounds.
Keywords: Ganoderic acid, Molecular docking, ADMET, Maestro
















Virtual High Throughput Screening to control the Rice blast disease caused by
Magnaporthe grisea and exploration of fungicides efficiency
Hima Vyshnavi.A.M, R.Chitra, K.Priyadharshini, N.Bharathi, J.Ramalingam.
Department of Plant Molecular Biology and Bioinformatics, CPMB&B, Tamil Nadu Agricultural
University, Coimbatore-641003, Tamil Nadu, India

Rice blast, caused by a fungus Magnaporthe grisea. It forms a specialized infection structure
called appresorium through which it invades the host plant and causes lesions on leaves, stems, peduncles,
panicles, seeds, and even roots. cAMP signaling pathway is found to be responsible for appresorium
formation and are likely to involve perception of signals through GPCRs. Among various subunits of
GPCRs, the beta subunit was reported to involve in multiple steps of infection related to morphogenesis in
Magnaporthe grisea. The present study targets beta subunit of GPCR, the inhibition of these proteins would
help to control the invasion of fungus. The fungicides which are currently used to control rice blast disease
are: Tricyclazole, pyroquilon and Tricyclic amides. In certain cases the fungal species develop resistance to
these chemical fungicides, hence the phytocompounds were selected from various sources and screened for
its antifungal activity against Rice blast by means of docking studies using GLIDE. This study would pave
the way for the development of novel fungicide against Rice blast disease. The efficiency of these small
ligand molecules was analysed based on the glide score and hydrogen bonding interaction with the target
protein.












Design, synthesis, photophysics and DNA damage of quinolone appended chalcone derivative
Himank Kumar
a
, Prasath R
b
., A. Chattapadhyay
b
, Ritika Joshi
a
, P. Bhavana
b
and Sujit Kumar Ghosh
a
*
a
Department of Chemistry, Visvesvaraya National Institute of Technology, agpur,Maharashtra,440010, India,
b
Department of Chemistry, BITS-Pilani K. K. Birla Goa Campus, Zuarinagar, Goa, 403726, India
E-mail: sujitju@yahoo.co.in

The design, synthesis, characterization and photophysics of a potential bioactive quinoline derivative ADMQ and
its interaction with calf-thymus DNA (ct-DNA) has been reported using experimental and theoretical spectroscopic
techniques. Absorption spectroscopy, steady state and time resolved fluorescence spectroscopy, NMR and FTIR
experimental spectroscopic techniques have been used along with the carcinogenicity/ cytotoxicity/ mutagenicity
screening test and DNA electrophoresis studies. The experimental observations have been rationalized theoretically
by density functional theory (DFT), ZINDO-CI molecular modeling calculations and molecular docking. The
environmental effects have been studied in ground and excited state in a variety of solvents of different polarity.
Photophysics of the molecule shows the intramolecular charge transfer in the excited state. The compound does not
exhibit any deleterious effect or toxicity to the bacterial cell in carcinogenicity /cytotoxicity/mutagenicity studies.
Agarose gel DNA electrophoresis has shown partial cleavage of DNA by this potential drug ADMQ. Interaction of
ADMQ with ct-DNA leads to dramatic decrease in the fluorescence intensity of the compound, suggests the
binding of ADMQ with ct-DNA. Induced fit docking (IFD) also supports the DNA binding. The experimental and
theoretical spectroscopic research describe herein could be very useful to assess the mechanistic details of chalcone
derivative in physiological conditions.

Keywords: ADMQ, Chalcone, Segmented linearity, Photophysics, Fluorescence quenching, Radiationless
deactivation, IFD etc.










Homology Modeling and Molecular Docking Studies of MenE (OSB-CoA Synthase) for Anti-
Tubercular Drug Development
A. Jerad Suresh*, K.M. Noorulla, R. Devi, P.R. Suriya
Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College, Park Town,
Chennai, Tamil Nadu.


MenE: OSB-CoA Synthase (O-Succinyl benzoic acid - CoenzymeA Synthase), which is involved in
the menaquinone biosynthesis in mycobacterium tuberculosis, seems to be a potential target. MenE
catalyzes the formation of OSB-CoA through a two-step reaction that proceeds via acyl-adenylate
intermediate & utilizes ATP & CoA as co-factors
1
. A target identification pipeline study for Mtb through an
interactome, reactome and genome-scale structural analysis shows that MenE passes through the filters such
as network analysis, flux balance analysis, genome-scale essentiality data, sequence analysis, structural
assessment, expression under various conditions, non-similarity to anti-targets, non-similarity to gut-flora
proteins, targets expressed during persistence and as broad-spectrum target
2
.
In our present study, a viable model of MenE protein is created by performing homology modeling.
It was stabilized by Molecular dynamics followed by the molecular docking in the identified target site with
our in-house database to identify promising candidates for tuberculosis.

Keywords: MenE, OSB-CoA, Mtb, homology modeling, docking

References:
1. Kwon O, Bhattacharyya DK, Meganathan R. J Bacteriol. 1996, 178(23), 6778-81.
2. Karthik Raman, Kalidas Yeturu and Nagasuma Chandra. BMC Systems Biology, 2008, 2, 109.










Aminoacid-specific Preferential Binding Site for Ligands A peptides to Rationalize
Drug Design for Alzheimers Disease
Harish S. Kundaikar, Mihir P. Khambete and Mariam S. Degani
*
Institute of Chemical Technology, N.P. Marg, Mumbai - 400019, Maharashtra, India
E-mail: *ms.degani@ictmumbai.edu.in

Alzheimers Disease (AD) is a progressive irreversible neurodegenerative disorder causing loss of reasoning
and ability to care for oneself, as seen increasingly in the geriatric populations. AD is characterized by
deposition of senile plaques composed of neurotoxic -amyloid (A) peptides. X-ray crystal structures of A
peptide fibrils are unavailable due to their difficulty in being crystallized for this technique, thus the binding
sites on these peptides are unclear. Knowledge of such binding sites could help in the development of agents
for AD. NMR solution structure of A peptides is, however, available and here we present our research
utilizing this NMR structure for binding to these peptides to decipher the binding site on the A peptides
using experimental data and molecular modeling techniques. Initially, the NMR solution structure was
studied with known ligands/inhibitors using molecular docking for analysis of binding sites, then induced fit
docking and further site mapping was pursued for cross-validation of one of these sites as binding site.
Quantitative analysis of interactions of individual residues by molecular mechanics and further molecular
dynamic simulations signify the relative importance of hydrophobic interactions over hydrogen bonding in
binding interactions with this binding site. Thus we propose an aminoacid-specific binding site on A
peptides which could help in understanding the interactions of known ligands with A oligomers. This
preferential binding site could be used in the rational design of A ligands with improved binding
characteristics for the diagnosis or therapy of AD.













E-2(armacop(ore Mapping and *ocking 'tudy of /'. 2rotein of !uman Influenza 1 &iruses3

Ishwar Chandra
~
, Abhisek K Behera, Sarah S Cherian*
Bioinformatics and Data Management Group, National Institute of Virology, Pune 411001, India.

Background: The general rapid appearance of Influenza virus strains resistant to known neuraminidase and
matrix protein inhibitors, Oseltamivir and Amantadine respectively, necessitates the development of newer
antivirals. The non-structural (NS1) protein of influenza virus is a multifunctional protein and confers
resistance to antiviral interferon (IFN) induction. The protein has two domains, the N-terminal (residues 1
73) RNA-binding domain
1
(RBD), and the C-terminal (residues 74230/237) effector domain
2
(ED). The
ED binds with the cleavage and polyadenylation specificity factor (CPSF30) and inhibits the production of
cellular mRNAs including IFN- mRNA. A large hydrophobic pocket on NS1 comprising of amino acid
residues K110, I117, I119, Q121, V180, G183, G184 and W187 interacts with the CPSF30. This
hydrophobic pocket could be explored to design potential antivirals that inhibit the binding with CPSF30.
Methodology: Crystal structure of influenza A NS1 protein ED (2RHK.pdb) was retrieved from protein data
bank. Energy-optimized structure-based pharmacophore features of potential ligands were obtained by
docking into the hydrophobic pocket of NS1 with the fragment library from Schrodinger using Glide XP
3
.
Based on the energy-optimized pharmacophore obtained, Phase
3
module of Schrodinger software suite was
used to screen Asinexs MedChem building blocks (a public database of about 7000 drug like compounds)
to find suitable hits.
Results: The resulting pharmacophore model contained an aromatic ring, an acceptor and two donor sites.
Using this model, 169 compounds were obtained on database screening and 130 compounds that yielded a
fitness score of more than 1.0 were further subjected to docking. Here we report the best five compounds
(IDs BAS 08978615, BAS 00337509, BAS 09627795, BAS 09627796, and BAS 09627799) based on their
docking scores. Moreover, the backbone structural scaffolds of these five compounds can be used to design
drug like compounds targeting the NS1 protein of influenza.

References:
1. Hale et al., (2008) JGV, 89: 2359-2376.
2. Das et al., (2008) PNAS, 105:1393-13098.
3. Glide (version 5.9), Phase (version 3.5), Schrdinger, LLC, New York, NY, 2013.








IN SILICO DRUG DESIGNING FOR TUBERCULOSIS
DIVYA PRIYA.S, KAVITHA
BHARATHIDASAN INSTITUTE OF TECHNOLOGY, ANNA UNIVERSITY, TIRUCHIRAPPALLI-620 024.
E-mail: divyapriya67ph@gmail.com

Tuberculosis remains one of the deadliest threats to public health. Every year two million people die of the
disease, which is caused by the microorganism Mycobacterium tuberculosis. Roughly one third of the
world's population is infected and more and more bacterial strains have developed resistance to drugs. A
protein called LipB is essential for the organism because it activates cellular machines that drive the
bacterium's metabolism. Protein is found in the cytoplasm of the cell. This three dimensional, jelly-like
lattice interconnects and supports the other solid structure. The cytosol is mostly composed of water and
many low molecular weight compounds. In eukaryotes, the cytoplasm also contains a network of
cytoplasmic filaments (cytoskeleton).It is a monomer and it contains 230 amino acids in it, LipB is highly
active in acutely infected cells. In these cells, a 70-fold increase in the production of LipB is seen compared
to other cells. General function of LipB is, it catalyzes the transfer of endogenously produced octanoic acid
from octanoyl-acyl-carrier-protein onto the lipoyl domains of lipoate-dependent enzymes. Lipoyl-ACP can
also act as a substrate although octanoyl-ACP is likely to be the physiological substrate LipB is a very
promising drug target, because it belongs to a vital pathway, unlike other organisms M. tuberculosis has no
backup mechanism that could take over LipB's role. This means that an inhibitor blocking its active site
would shut down key processes the bacterium needs to survive and replicate. This would be a very effective
strategy for a drug. This strongly indicates an involvement in pathogenesis and makes it a particularly
interesting target where traditional drugs have lost their efficacy. Hence, my present case study deals with
docking studies of LipB protein using software to find out the binding mode of ligands.























InSilico Screening of Potential Inhibitors against Dengue Virus

Nishandhini.M
1
, Suganya . J
2
, Radha Mahendran
1*
Department of Bioinformatics, Vels University, Chennai-600 117

Dengue virus (DENV) is the most prevalent mosquito transmitted viral infection affecting 2.5 billion
people across the globe and it belongs to family Flaviviridae. NS3(Non Structural protein 3) is a
multifunctional protein of 618 amino acids that functions both as a chymotrypsin like serine protease as well
as an RNA helicase and RTPase/NTPase. It plays an important role in controlling the dynamics of viral
protein translation versus RNA replication by controlling the availability of viral proteins. However, there is
neither vaccine nor effective antiviral drugs to treat dengue virus infection. Many studies have been
conducted for exploring the antiviral activity of chemical compounds against DENV. Among these
compounds, some are small molecules that can inhibit specific steps of viral intracellular replication or
effect at viral proteins. Thus, we have made an attempt to study whether potentially active plant compounds
can serve as effective anti dengue agents. Dengue NS3 structure (2VBC) was retrieved from Protein data
bank. Antiviral agents from Natural product library (NCBI-PUBCHEM) have been screened by docking
study for NS3 structure. Docking results revealed that all inhibitors studied in this work have hydrogen bond
interactions with Arginine and Lysine residues that play a central role in viral replication. This study will be
further implemented in future drug designing.

Keywords: Dengue virus (2VBC-DENV), Antiviral agents, Natural plant inhibitors, Docking.




A RATIONALE SEARCH OF NEW LEADS FOR ANTI-TUBERCULAR DRUG DESIGN

JAHEER AHMED SHAIK, M MURALI KRISHNA KUMAR, Andhra University, Vizag, 530003
Tuberculosis, caused by Mycobacterium tuberculosis is a debilitating disorder affecting millions of
people every year. A total of less than eight drugs are available throughout the world as first line treatment
for successfully sterilizing the patients. An inevitable long duration of therapy, large doses and toxic effects
leads to patient noncompliance, resulting in development of drug resistance, which is steadily rising right
now. This problem can be solved via discovering molecules with novel chemistry & mechanism of action.
So as to avoid cross resistance & synergistic potentiating of treatment regimen. Urease, an ubiquitous
enzyme present in all soil bacteria is highly essential for survival of microbes. Urease enzyme of
Mycobacterium tuberculosis (MTB) was studied to only a very limited extent. This presentation deals with
modeling of urease enzyme of MTB, docking & lead identification process.

Key words: Mycobacterium tuberculosis, urease, docking, lead identification.

















Docking studies of C-2/C-5/C-6 modified NeuNac analogues-Cholera toxin complex

Jino Blessy.J* & D. Jeya Sundara Sharmila
Department of Bioinformatics, Karunya Univesity, Karunya Nagar, Coimabtore-641114

Email: blessyjino@gmail.com

Pathogenic microorganisms are resistance towards antibiotics. Recent studies revealed that notorious
pathogens such as Vibrio cholerae have acquired multiple drug resistance and the treatment became a
serious concern. Present study investigates the utility of computer aided method to study the mechanism of
receptor-ligand interactions and thereby inhibition of virulence factor cholera toxin of Vibrio cholera by
novel synthetic sialic acid (NeuNac) analogues. NeuNac with multiple modifications at different position
(C-2/C-5/C-6) are investigated by molecular docking using glide v5.7. Cholera toxin protein structure 3CHB
was optimized in Maestro v9.2. Thirty one NeuNac analogues are substituted in different position and
docked against 3CHB cholera toxin protein. Among the 31 analogues 8 of them showed least XPG docking
scores, 2-d-2Heq-1 -decarboxy-1 -phosphono-Neu5Ac of -8.96 Kcal/mol, 2-d-2H
eq
-7-epi-Neu5Ac of 8.85
Kcal/mol, 2-d-2Heq-8-epi-Neu5Ac of -8.63 Kcal/mol, Methyl--KDN of -8.48 Kcal/mol, 2-d-2H
eq
-7,8-epi
2
-
Neu5Ac of -8.19 Kcal/mol, 2-d-2H
eq
-Neu5Ac of -8.10 Kcal/mol, 2-d-2H
ax
-Neu5Ac -8.07 Kcal/mol, Methyl-
-5-azido-5-d-KDN of -8.06 Kcal/mol. The NeuNac analogues-Cholera toxin complex explain that the
NeuNac analogues block the active site residues TYR-12, HIE-13, ASN-14, GLN-56, HIE-57, ILE-58,
TRP-88, ASN-90, LYS-91 directly through intermolecular hydrogen bonding. Therefore NeuNac analogues
can be considered for designing drug molecules against cholera toxin.











Design and Molecular Modelling of Direct Inhibitors of Mycobacterium Enoyl Co-A Reductase
(InhA) as Potential Antitubercular Agents
Joshmi Joseph*, Gurubasavaraj Pujar

Department of Pharmaceutical chemistry, JSS College of pharmacy, JSS University, Mysore-570015,
Karnataka

Tuberculosis is more prevalent in the world today than at any other time in human history. Mycobacterium
tuberculosis is the pathogen responsible for TB and the emergence of multidrug resistant strains of
Mycobacterium tuberculosis makes the discovery of new molecule scaffold a priority. Recently, di-phenyl
ether nucleus has emerged as a promising scaffold to direct inhibitors of mycobacterium enoyl Co-A
reductase (InhA) enzyme from anti-tubercular activity of triclosan. These direct InhA inhibitors require no
mycobacterial katG enzymatic activation and thus circumvent the resistance mechanism to anti-tubercular
prodrugs such as INH and ETA that is most commonly observed in drug-resistant clinical isolates. In efforts
to perform structure based studies for di-phenyl ether derivatives, we designed 136 novel di-phenyl ether
derivatives based on the structural features of triclosan. Molecular docking studies of the designed 136
molecules were carried out on Enoyl-Acyl Carrier Protein Reductase (InhA) (PDB:2OOS) of
Mycobacterium Tuberculosis using Schrodinger Molecular Modeling software (GLIDE). Out of the docked
molecules, 10 have shown good docking score and binding interactions when compared to the standard
Triclosan molecule (G score: -9.1) and the extracted ligand, A_1 2OOS (G score: -11.2). Compound 104
showed interactions with important amino acids of InhA i.e Tyr267 and Ala217. The compounds with good
docking score will be undertaken for their synthetic suitability and evaluation of anti-TB activity. These
molecules can be used for development of next generation direct InhA inhibitors.





KEYWORDS: Di-phenyl ether derivatives, Docking, Anti-tubercular
activity


O
Cl Cl
Cl OH
Triclosan

COMPREHENSIVE FRAGMENT BASED TECHNIQUE FOR THE DESIGN OF NOVEL DHFR
INHIBITORS

O M Deepak, Krishnapriya A S, Aparna Nair and Krishnan Namboori P K
Computational Chemistry Group, Computational Engineering and Networking, AMRITA Vishwa
Vidyapeetham, Amritanagar, Coimbatore-641112
E-mail: n_krishnan@cb.amrita.edu

A comprehensive fragment based drug designing strategy has been adopted in this work to identify novel
inhibitors for target DHFR enzyme as promising anti-cancer drugs. In cell cycle, folate is necessary for the
production and maintenance of new cells, for DNA synthesis, RNA synthesis and preventing changes to
DNA [1]. The folate is converted to tetrahydrofolate with the help of DHFR enzyme and the over expression
of the process leads into cancer. Common anti-folate drug, which has been used for years in the treatment of
various cancers such as colorectal and breast cancer is methotrexate. Methotrexate inhibits dihydrofolate
reductase, and thus preventing purine and pyrimidine synthesis, which accounts for its efficacy in the
therapy of cancer as well as for some of its toxicities [2].
In modern drug development, the computer aided drug design (CADD) has been accepted and appreciated
as an essential designing phase. Among various techniques used in CADD, a three dimensional structure
based de novo design strategy has come up as a major leading procedure [3]. The method involves
identification of hotspot or the binding site of the target by Computational Site Identification by Ligand
saturation technique. Then the pharmacophoric or drug template is identified from the hot spot of the target
following FBDD method. By proper scoring and filtering using interaction energy, pharmaco dynamic and
pharmaco kinetic attributes most suitable template has been identified. The template is optimized for all
target molecules by suitable fitting technique [4]. From the optimized and most suitable template, ligand
molecules are generated by evolving the molecule within the binding pocket of the target [5]. The identified
ligands are further evaluated to study their effectiveness in functioning as anticancer drugs by computing
ligand efficiency, fit score, lipophilic efficiency, IC50, and relative enrichment factor. The properties have
been compared with respect to standard anti cancer drugs. Seven potential leads have been identified, which
exhibit good level of interactions with the target proteins. These selected new ligands help to inhibit the
DNA synthesis and thus leading to the cell to apoptotic pathway, subject to further in vivo and in vitro
evaluation [6].

References
1. Z. Hilal, R. Anwar, K. Omar, and S. Bashar, Cancer Treatment by Greco-Arab and Islamic Herbal
Medicine, The Open Nutraceuticals Journal, vol. 3, pp. 203-212, 2010.
2. A. Alexander and M. Maria, Fragment-Based Drug Discovery: What has it Achieved so Far,
Current Topics in Medicinal Chemistry, vol. 7, pp. 1544-1567, 2007.










Identification and structure based design of specific CDK5 inhibitors for the treatment of
neurodegenerative disorders

K.V. Dileep, C. Remya and C. Sadasivan*

Department of Biotechnology and Microbiology and Inter University Centre for Bioscience, Kannur
University, Thalassery campus, Palayad P.O., Kerala 670 661,
E-mail: csadasivan@gmail.com
Alzheimer's disease is an age dependent cognitive decline due to loss of neurons at the cortex and
hippocampus. Extracellular senile plaques formed by the accumulation of amyloid- (A) and intracellular
neurofibrillary tangles (NFTs) are the pathological hallmarks of AD. Large number of neuronal insults such
as oxidative stress and inflammation are considered to be the upstream events in AD. Recent studies
suggested that AD brains have an increased activity of Cyclin Dependant Kinase 5 (CDK5). This may lead
to the hyperphosphorylation of a microtubule associated tau protein and causing it to aggregate as NFTs.
CDK5 is a serine/threonine kinase enzyme, normally expressed in the brain. It plays an essential role in the
development of the central nervous system during mammalian embryogenesis. Since the over-expression of
CDK5 is associated with AD, inhibition of the enzyme is considered to be an effective approach for the
treatment of neurodegenerative disorders. To avoid unwanted side effects, an inhibitor specific to CDK5,
which does not inhibit other CDKs is preferred.
In the present study, an attempt was made to identify specific CDK5 inhibitors using in silico tools. Initially
CNS data set of Chembridge (55649 compounds) was collected and ADME filters were applied to select
compounds with bioavailability and ability for blood brain barrier penetration. Parameters such as CNS
activity, polar surface area, MDCK and Caco cell permeability were also taken into the consideration. Total
11000 compounds which satisfy the conditions were docked into the active sites of 10 different CDKs (CDK
1 to 10). Molecular structures of CDK 2, 3, 4, 5, 6, 7 and 10, were downloaded from PDB and the structures
of CDK 1, 8 and 9 were built using homology modeling.
The compounds which bind preferentially to CDK5 were selected based on the Glide score. In order to
enhance the binding affinity, structural modifications of the compounds were made. Induced Fit Docking
onto the CDKs was carried out using the designed compounds. A 5 ns MD simulations were also carried out
in order to determine the stability of the binding. An in silico based QSAR analysis was carried out for the
designed compounds and the results were compared with that of known CDK5 inhibitors. The details of the
results will be presented.








Insilico drug discovery from Cyanobacteria
Dr. S. Vijayakumar and Dr. M. Menakha
Department of Botany and Microbiology, A.V.V.M. Sri Pushpam College (Autonomous), Poondi, Thanjavur
Dt. Tamil Nadu


Marine microorganisms have been little studied for their application to human needs. Early research
into marine microorganisms was concerned largely with their physiology, photosynthetic capacities, and
potential antibiotic and toxicological properties. Marine microorganisms might also be explored with for
discovering new compounds with other therapeutic roles, importantly like anti inflammatory property. These
areas of research remain significant, particularly in view of the development of techniques enabling culture
of marine bacteria on large scales. The prokaryotic marine cyanobacteria continue to be an important source
of structurally bioactive secondary metabolites. Over 300 nitrogen-containing secondary metabolites,
represented by diverse structural types, have been reported from marine cyanobacteria. A majority of these
metabolites are biologically active. Most of them are with anticancer properties. Computer aided molecular
docking plays an important role in the design of new drug leads. Conventional methods of drug discovery
are very expensive and time consuming. Computer aided molecular docking methods for drug discovery are
economic and faster than conventional methods. Docking is frequently used to predict the binding
orientation of small molecule drug candidates to their protein targets in order to in turn predict the affinity
and activity of the small molecule. Hence docking plays an important role in the rational design of drugs.
Because of the biological and pharmaceutical significance of molecular docking, considerable efforts have
been directed towards improving the docking methods. In the present study Schrodinger suite programme
were used. Thus it is concluded that the utilization of cynobacteria will help for the development of new
drugs for various diseases.








In-Silico design and study of novel Benzopiperidines as HIV-1 Reverse Transcriptase Inhibitor
Subhash Chander*, Ashok Penta and Sankaranarayanan Murugesan

Department of Pharmacy, Birla Institute of Technology & Science, Pilani-333031. Rajasthan. India
E. Mail: subhashsaininiper@gmail.com

Reverse Transcriptase (RT) Inhibitors are promising anti-HIV drugs, currently available as Nucleoside /
Nucleotide Reverse Transcriptase Inhibitors (NTRIs) and Non-nucleoside Reverse Transcriptase Inhibitors
(NNRTIs) in the market. Non-nucleoside Reverse Transcriptase Inhibitors are the key component of Highly
Active Anti-retroviral Therapy (HAART) and they preferred in combination with NRTIs over protease
inhibitors (PIs), because of their high selectivity, less toxicity and synergistic inhibition of enzyme with
NRTIs. Long-term clinical effectiveness of approved NNRTIs like other anti-HIV drugs has been hampered
due to the rapid development of drug resistance. In the present study, we have designed 8 novel series of
bezopiperidine (containing 140 different analogues) as Non-nucleoside inhibitors of HIV-1 Reverse
Transcriptase based on the pharmacophoric requirements. In-Silico docking studies of the designed
analogues have done against both drug sensitive wild HIV-1 Reverse Transcriptase (RT) (PDB ID: 3MEE)
and drug resistance mutated HIV-1 RT (PDB ID: 3TAM & 4I2Q) by using molecular docking software
GLIDE in extra precision mode. Among the selected drug resistance strains, receptor protein (PDB ID:
3TAM), has mutation at K103N, (frequently encountered mutation during NNRTIs therapy) which is
resistant to first line NNRTIs Nevirapine and Delaviridine. Second mutated receptor protein (PDB ID 4I2Q)
is dual mutated at K103N and Y181C, which is resistant to almost all first and second generation NNRTIs
except Rilpivirine. Among the designed analogues, around twelve compounds showed significant in-silico
activity against the wild RT strain (3MEE), and thirty eight analogues exhibited good activity against
K103N variant RT (3TAM). In addition, nineteen compounds retained in-silico activity against dual mutant
RT (4I2Q). Among the all designed analogues, three compounds 51b, 51x and 52x retained activity against
all the three variant forms of HIV-1 RT. These three analogs are selected and used for further in-silico
absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction studies using Quickpro
module of Schrodinger software, AdmetSAR and Toxpredict online tools. Cross-docking on variant forms
of RT and ADMET prediction studies, may helpful in the design of novel anti-HIV agents active against
both wild-type and drug resistant strains.
















DOCKING and EXPERIMENT











IMPROVED SMALL-MOLECULE INHIBITOR OF THE ZINC ENDOPEPTIDASE OF
BOTULINIUM NEUROTOXIN SEROTYPE A
S.JAYA BHARATHI,
BHARATHIDASAN INSITUTE OF TECHNOLOGY, ANNA UNIVERSITY, TIRUCHIRAPALLI-620 024
E-Mail: jayabharathisivaprakasam@gmail.com


Optimization of a serotype-selective, small-molecule inhibitor of botulinium neurotoxin serotype A
(BONTA) endopeptidase is a formidable challenge because the enzyme-substrate interface is unusually large
and the endopeptidase itself is a large, zinc-binding protein with a complex fold and based on the
computational results, it is hypothesized that introducing a hydroxyl group to the inhibitor could improve its
potency. Synthesis and testing of the hydroxyl-containing analog as a BONTA endopeptidase inhibitor
showed a twofold improvement in inhibitory potency with a small increase in molecular weight (16 Da).



















Computational repurposing and experimental validation of FDA approved drugs for HIF-Prolyl
Hydroxylase inhibition

Mahesh Kumar Teli and Rajanikant G. K.
School of Biotechnology, National Institute of Technology Calicut,
Calicut - 673601, Kerala, India

HIF stability and activation are governed by a family of dioxygenases called HIF prolyl-4-hydroxylases
(PHDs). It has been identified as a new target to augment the adaptive machinery that governs
cytoprotection in disorders associated with ischemia/reperfusion, inflammation and oxidative stress. The
present work plan aims at giving new purpose to some well-established FDA-approved drugs. Exploiting
drug polypharmacology to identify novel modes of actions for drug repurposing has gained significant
attentions in the current era of weak drug pipelines. Here, we propose that by combining the literature
survey, docking and manual interpretation altogether, we were able to perform virtual screening on FDA
approved drugs to identify potential PHD inhibitors. Upon screening of FDA approved drugs, a final set of 6
hits were selected for experimental testing. All the six drugs were divers and immune-blotting was carried
out to evaluate their ability to up-regulate HIF, in order to validate our hypothesis. Out of six, three drugs
showed significant up-regulation of HIF possibly by inhibiting the PHD. It is believed that the appropriate
use of the literature survey, docking, manual interpretation and experimental validation strategy in drug
design process should improve the ability to identify hits and confirm their potential to serve as basis for
drug repurposing.











Synthesis, In-Vitro, In-Vivo Evaluation And Molecular Docking Of 2-(3-(2-(1, 3-Dioxoisoindolin-2-Yl)
Acetamido)-4-Oxo-2-Substituted Thiazolidin-5-Yl) Acetic Acid Derivatives As An Anti-Inflammatory
Agents.
Anna Pratima Nikalje
a
, Nazma Hirani
a
, Mangesh S. Ghodke
a
, R. Nawle
b
, H. Une
c
, S. Bari
d
a
. Department of Pharmaceutical Chemistry, Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus,
Rauza Bagh, P.B. No. 33, Aurangabad-431001, Maharashtra, India.
b.
Department of Pharmacology, Government College of Pharmacy, Aurangabad-431001, Maharashtra,
India.
c.
Department of Pharmacology, Y.B. Chavan College of Pharmacy, Aurangabad.
d.
Department of Pharmaceutical chemistry,
1
.R C. Patel College of Pharmacy, Shirpur.
* Email: ana@k.st



A series of novel 2-(3-(2-(1,3-dioxoisoindolin-2-yl) acetamido)-4-oxo-2-phenylthiazolidin-5-yl) acetic acid
derivatives 5 (a-l) have been synthesized by cyclo condensation of (E)-N'-substituted
benzylidene/methylene-2-(1,3-dioxo isoindolin-2-yl) acetohydrazide 4 (a-l) with mercapto succinic acid , in
dimethyl formamide as solvent, using anhydrous zinc chloride as catalyst in Microsynth microwave reactor.
The synthesized compounds were evaluated for anti-inflammatory activity using in vitro and in vivo model.
Furthermore, ulcerogenic toxicity study was performed for selected compounds. All the compounds have
shown promising anti-inflammatory activity in both the models. Docking studies were performed to know
the binding affinity of these derivatives towards the human serum albumin (HSA).



















Design and Synthesis of some novel biologically active 3.5-disubstituted 1, 2, 4-triazole incorporated
2-mercaptobenzothiazoles
Naga Srinivas Tripuraneni*, Md Afzal Azam
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Ooty, Udhagamandalam, Tamilnadu

Inflammation though one of the innate immunity responses continues to be a challenge due to the complex
biological pathways. Due to dose limiting toxicities and ulcerogenic potency there is a lacuna of a suitable
anti-inflammatory drug and the further biochemical complexity and location of PDEs made it more difficult
for selective PDE inhibitors. Therefore, in an attempt to identify safe and potent anti-inflammatory drug
candidates novel drug like molecules were synthesized by linking 1,2,4-triazoles and 2-
mercaptobenzothiazoles.The potent molecules (Hits) virtual high throughput screening was performed using
Schrodinger Drug design Suite on PDE4B receptor. The crystal structure of PDE4B is obtained for RSCB
Protein data bank (PDB ID: 1XM4). Plausible compounds were identified (virtual hits). Molecular
modelling studies predicted that the compounds 5f, 5g, 5h, 5i and 5c possess good docking affinity with the
PDE4B receptor and further, these molecules were subjected to anti-inflammatory studies in rats by
carrageenan induced rat paw oedema model and further the ulcerogenic index is also calculated. The data of
docking study, anti-inflammatory study and ulcerogenic index will be presented.












STUDY OF 4-(ACETYL AMINO)-N-[2-(2,4-DIMETHOXYPHENYL)-4- OXO-1,3-THIAZOLIDINE-
3-YL] BENZAMIDE AND ITS DERIVATIVES AS POTENT INHIBITORS OF COX-1:
DISCOVERY OF NEW ANTI-INFLAMATORY DRUGS
Priyam Thakor
*
, AniLkumar N, Antriksh Patel, N.V.Kalyane, R.B.Kotnal
Department of Pharmaceutical Chemistry, BLDEAs College of Pharmacy, BLDE University campus,
Bijapur-586103, Karnataka, India

email: priyamthakor@gmail.com

The discovery of two forms of the cyclooxygenase enzymes, COX-1 and COX-2, and the development of
COX-2 specific inhibitors as anti-inflammatory and analgesics have offered great promise that, the
therapeutic benefits of NSAIDs could be optimized thorough inhibitors of COX-2. This research is focused
on the effect of the anti-inflammatory N-acetylcysteine (NAC) on the inhibition of prostaglandin E2
formation in activated monocytes by specific and non-specific COX inhibitors. We found that
lipopolysaccharide induced prostaglandin E2 formation was significantly reduced by rofecoxib and by
diclofenac, two NSAIDs.
The Ligand structure is 4-(acetylamino)-N-(2-(2, 4-dimethoxyphenyl)-4-oxo-1,3-thiazolidin-2-yl)
benzamide used in docking. Virtual screening was performed on the basis of structural similarities, research
isomers & conformers. If we are making structures in chemsketch then we save it in Extended mol. format
.Now, when the structure of ligand is drawn and saved to the disk then we open the software Open Babel
GUI 2.0.2 which is used to convert the Extended mol. files to pdb files. After converting pdb files, this file
will use for further work and analysis using Autodock 4.
Study of molecular docking of molecules, synthesize some new N-[2(4-methoxyphenyl)-4-oxo-1, 3-
thiazolidin-3-yl] pyridine-4-carboxamide. This compound was evaluated for their possible biological and
pharmacological properties. The compounds were characterized by their melting point, TLC, IR, NMR and
Mass spectral studies.
Docking was carried out for 4-thiazolidinone with conformers 4-(Acetylamino)-N-(2-(2,4-
dimethoxyphenyl)-4-oxo-1,3-thiazolidin-2-yl)benzamide and its derivatives show minimum Binding Energy
Range -11.43 to -3.36. The corresponding ligands which we have found out were matched for the Lipinskis
rule of 5 parameters and the results showed that, the 20 molecules show some extraordinary results out of
500 molecules. All the synthesized compound have been evaluated for anti-inflammatory (in-vitro) studies
the test compound (N-[2(4-methoxyphenyl)-4-oxo-1, 3-thiazolidin-3-yl] pyridine-4-carboxamide) A
1,
which
showed inhibition of 82% of albumin denaturation compared to standard drug and the anti-inflammatory (in-
vivo) studies the test compound A
1
which show inhibition of 65% of edema compare to standard drug







In silico designing and validation of a potential small molecule inhibitor against AphB, a virulence
gene activator from Vibrio cholerae
Rahul Shubhra Mandal
1
, Atri Ta
2
, Mohsina Tasneem
1
, Santasabuj Das
1,2*

1
Biomedical Informatics Center,
2
Division of Clinical Medicine, National Institute of Cholera and Enteric
Diseases, Kolkata - 700010, India
Vibrio cholerae is the causative agent of cholera, a severe waterborne diarrheal disease. Worldwide, it
affects 35 million people and causes 100,000130,000 deaths a year as of 2010. Antibiotics are available
that decrease the disease severity and duration of cholera. However, search for alternative therapies are
important to avoid the emergence of drug resistance. Toxin-coregulated pilus (TCP) and cholera toxin (CT)
are the two major virulence factors that are critical for pathogenesis of V. cholera in humans. Their
expression is initiated at the tcpPH promoter by the AphA and AphB regulators. AphA is a winged-helix
DNA-binding protein that enhances the ability of AphB, a LysR-type transcriptional regulator (LTTRs), to
activate tcpPH expression. Like other LTTRs (TsaR and BenM), AphB also possess a ligand-binding pocket
at the interface of RD-I and RD-II regulatory domains (RD) consisting of residues important for the
regulation of tcpPH expression. Ligand binding is reported for TsaR and BenM, but there is no ligand
reported for AphB which may bind to its active site pocket. Here we have taken an in silico approach to
design a small molecule inhibitor of AphB that blocks the expression of tcpPH promoter. As there is no
previous knowledge about the small molecule ligand, we have used LUDI program of Discovery Studio 2.5
to generate a small molecule ligand, which fits best into the AphB active site and also interact with the
critical residues within the pocket that are important for its activity. Subsequently, this starting molecule was
used for screening various small molecule databases like PubChem, ZINC etc. to create a dataset of similar
molecules for the purpose of further screening. Virtual screening of these small molecules was carried out
using GLIDE 5.8 docking program integrated in Schrdinger suite 2012. The resulted molecules were
further shortlisted by analyzing the interaction with binding site residues and binding free energy. Finally
selected molecules were evaluated by Molecular Dynamics (MD) simulation in GROMACS and studied for
their inhibitory role in mice models. One of the molecules inhibited the colonization of Vibrio cholerae O1
biovar eltor str. N16961 in suckling mice intestine and helped them to survive by significantly reducing
diarrhoea. This molecule also reduced cholera toxin secretion by the above strain, which was proved by the
rabbit ileal loop assay.











Developing new leads as anti-tubercular agents that target novel biological target of
Mycobacterium tuberculosis
Ravindra D. Wavhale
a
, Premlata K. Ambre
a
, Raghuvir R.S. Pissurlenkar
a
, Dhiman Sarkar
b
, Manoj
Avaghade
b
, Evans Coutinho
a
*.
Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Mumbai-400098, India
a

CombiChem Bio Resource Center, Organic Chemical Division, National Chemical Laboratory, Dr. Homi
Bhabha Road, Pune, Maharashtra 411008, India
b.
Email:evans@bcpindia.org*
Tuberculosis (TB) has been declared a global health emergency by the world health organisation (WHO). In
the last decade, Mycobacterium tuberculosis glutamine synthetase (MtGS) a key enzyme for nitrogen
metabolism has emerged as a potential target. The majority of known glutamine synthetase (GS) inhibitors
are simple amino acid (glutamate) analogues e.g. methionine sulfoximine and phosphinothricin which are
non-specific and non-drug-like molecules. Out of three different substrate binding sites of MtGs, a
significant difference is found in the nucleotide (ATP) binding site of MtGS and human glutamine
synthetase (hsGS). This provides the best opportunity to design GS specific inhibitors against
Mycobacterium tuberculosis.
The available crystal structure of MtGS bound to ADP (PDB code 2BVC) and with inhibitors (PDB code
2WGS, 3ZXR, 3ZXV, and 4 ACF) gave the insights of ATP binding site, provided important information
regarding key residues necessary for binding of substrate and inhibitor with enzyme. Amino acids Ser
280
,
Lys
361
, Tyr
230
and Glu
214
involved in hydrogen bonding with the substrate and inhibitor. Based on this
information novel inhibitors were designed containing different heterocyclic cores like imidazopyridine,
benzimidazole, imidazole and pyrrolo[2,3-d]pyrimidin. Designed molecules were further selected for
synthesis based on their interactions with MtGS, binding energy scores and drug like properties. Structures
of synthesized compounds were confirmed by characterizing with
1
H NMR and IR. All of these molecules
were evaluated for in-vitro MtGS inhibition.







Dopamine--hydroxylase as a novel drug target for cardiovascular diseases: In silico dentification
and in vitro validation of novel inhibitors
Sanjay Kumar Dey
#
, B.K. Thelma
$
, Suman Kundu
#

Department of Biochemistry
:
an% Genetics
;
, University of De(hi South 'ampus, Benito <uare= 2oa%, 4e> De(hi
++##?+, In%ia

/uman dopamine Q3hydroxylase 5h*B/6, expressed in noradrenergic ner,e terminals o7 ner,ous system as 9ell as in
chroma77in cells o7 adrenal medulla, is a key constituent o7 catecholamine 8iosynthetic path9ay. "s such *B/ has
8een implicated as an important drug target, 9hose inhi8ition could help the treatment o7 hypertension and cardiac
heart 7ailure. Since cardio,ascular mal7unctions are maLor causes o7 mortality and mor8idity in .ndia and a8road, it is
important to design no,el drugs to treat the 7atal disease. Existing *B/ inhi8itors are too 7e9, o7ten result in side
e77ects and are 7re:uently non3responsi,e to speci7ic population. Structure 8ased rational drug design has 8een
elusi,e so 7ar since no three3dimensional structure existed 7or 7ull3length h*B/. Ie ha,e sol,ed this pro8lem 8y
8uilding an in si(ico model 7or h*B/ that 9as ,alidated against experimental data 5-apoor et a(., ?#++, &8oS /ne6.
;he model 9as thus used in "utodock, #accoon, @lide SP and HP so7t9are 7or structure 8ased ,irtual screening
against se,eral small molecule data8ases including *i,ersity sets 7rom $ational ancer .nstitute, 0S", E.$ natural
compound data8ases, S.@%" %yria Screen Set, hemBank and (E@@. ;he docked structures 9ere then scored using
"utodock, HScore and Prime %%@BS" 5Schrodinger .nc., 0S"6. #esults o7 the multi3so7t9are 8ased ,irtual screen
ha,e suggested M& compounds as prospecti,e inhi8itors o7 *B/. ;he lead compounds 9ere then tested in vitro
against puri7ied 8o,ine *B/ 59ith &PR se:uence homology to human *B/6, 9ith the kno9n inhi8itor disul7iram as a
positi,e control, re,ealing ' compounds to 8e potent inhi8itors o7 *B/. In si(ico pharmacokinetic study using 1ikProp
module o7 Schrodinger .nc., 0S", has re,ealed ' leads to 8e latest generation o7 *B/ inhi8itors ha,ing ,ery high cell
permea8ility and ina8ility to cross the Blood Brain Barrier. En2yme inhi8ition assays con7irmed that these inhi8itors
had kinetic parameters suita8le 7or in vivo e,aluation. ;he 8inding o7 the inhi8itors to the en2yme 9ere ,alidated
8iophysically using 0)3,isi8le, 7luorescence and * spectroscopy as 9ell as .;. "ssessment o7 cellular tolera8ilities
and immune3toxicities against these lead compounds has sho9n promising results moti,ating us to proceed to9ards
their e,aluation in model animal systems. om8i@lide and <igand Based ore /opping 5Schrodinger .nc., 0S"6
methods ha,e 8een employed to optimi2e the lead compounds computationally, 7or 7urther chemical synthesis and
in vitro testing.
Reference: Kapoor A.; Shandilya M.; Kundu S., Structural Insight of Dopamine -Hydroxylase, a Drug
Target for Complex Traits, and Functional Significance of Exonic Single Nucleotide Polymorphisms. PLoS
ONE 6 (10): 2011, e26509.







Modeling, Synthesis and Characterization of Phosphopentapeptide A candidate substrate for Assay
of Calcineurin
Saraswathi R, Harish B.M. Gopi A, Anushree and Devaraju K.S.
Dept. of Microbiology & Biotechnology, Jnana Bharathi Campus,Bangalore University, Bangalore- 560-
056
E-mail: ksdevarju@bub.ernet.in

The measurement of Calcineurin (CN) activity plays an important role in understanding the mechanism
underlying many pathological conditions like cancer, metabolic aberrations and neurodegenerative
disorders. Current assay methods for CN are relative measurements which involve the use of CN or protein
phosphatase inhibitors. Hence, there is a need of CN specific assay without employing inhibitors for protein
phosphatases. Therefore the current study focused on modeling specific phospho peptides generated from
protein kinase A regulatory sub unit type II and docking them with CN using Molgro Virtual Docking
software. Further the candidate phospho pentapeptide was synthesized employing Fmoc method, purified
over HPLC and characterized by MASS spectrometry. This phospho pentapeptide was used for in vitro
assay of CN by malachite green method and the results compared with R II peptide which is a conventional
substrate used for CN assay. Docking study results indicate that phospho pentapeptide has higher binding
affinity to CN compared to R II and therefore it was employed as a substrate in the assay system, the in
vitro studies provides comparable results with RII peptide by Malachite green assay method.

















LIGAND DOCKING AND FRAGMENT-BASED PHARMACOPHORE BIVARIATE APPROACH FOR SCREENING OF
POTENTIAL DENGUE VIRUS INHIBITORS
Sindhoora Bhargavi Gopala Reddy
1,2
, Koji Ichiyama
2
, Emelyne Quek Jiang Li
2
, Youichi Suzuki
2
, Geetha
Mahadevappa
3
, Naoki Yamamoto
2
, Haraprasad Nanjundappa
1*
1 Department of Biotechnology, Sri Jayachamarajendra College of Engineering, Mysore, Karnataka, India
2 Translational Infectious Diseases Laboratory, Department of Microbiology, Yong Loon Lin School of
Medicine, National University of Singapore, Singapore
3 JSS Hospital, Mysore, Karnataka, India
E-Mail: nharaprasad@hotmail.com
Dengue fever (DF) is a mosquito-borne viral disease, caused by the Dengue Virus (DENV), an RNA virus
of the family Flaviviridae. DF has neither a specific treatment nor a vaccine. Hence, there is a constant need
to find an effective drug/vaccine as 40% of worlds population is at risk of infection. Current practices in
screening compound libraries for drug candidates involve either high throughput cell or enzyme based
assays and/or in silico screening by receptor-ligand library docking. While the in vitro approach is time
consuming and labour intensive, the conventional in silico methods suffer from inaccurate and inconsistent
prediction of binding poses, and results that do not often translate when tested in vitro.
Here, we report an improved method of computational screening of an FDA approved compound library for
identification of probable inhibitors of dengue viral proteins. A site points-centered grid was constructed at a
potential drug-binding site in the DENV protease complex. Initial screening was performed by Glide HTVS
docking of the compounds in the grid, and the results were enriched by SP and XP docking. In a receptor-
focused approach, the library was subjected to a second screening, to filter conformers that matched the site-
specific fragment-based pharmacophore hypothesis by using the Energy-optimized Structure-based
Pharmacophore (e-PCP) protocol. In this, a diverse fragment library was docked in the same grid as the
initial screening to generate PCP features after volume clustering of the docked poses of fragments. These
PCP features were then ranked based on the Glide XP-derived energetic values for their constituent atoms,
and using the best PCP features; several hypotheses with different matching rules were generated. The
hypotheses were then screened against the library for matches, which were further overlapped with glide XP
output from the first screen to produce higher enrichment of leads. In vitro studies of these enriched leads
further showed promising results as inhibitors of dengue virus. Hence, this method is better suited for
screening than conventional docking strategy alone. Bivariate screening method effectively uses the
potentially best druggable features of the receptors to identify compounds that bind with high affinity, as
well as interact with the predicted critical pharmacophoric features of the receptor. Apart from that, the
method adopted in the study gave nearly 4.5 times better enrichment when compared with univariate
method. However, the robustness of the method still needs to be explored.








Molecular docking guided structure based design of novel HIV-1 entry inhibitors.
Ramakrishna Munnaluri, Sree Kanth Sivan, Radhika Vangala, Vijjulatha Manga*
Molecular modeling and Medicinal Chemistry Group, Dept. of Chemistry, Nizam College, Osmania
University, Hyderabad 500001.
HIV-1 cell entry is mediated by sequential interaction of envelope proteins gp120 with the receptor CD4 and
co-receptor CCR5/CXCR4 on host cell. Binding of gp120 to CD4 and co-receptor triggers the release of
HIV-1 gp41, which undergoes a large conformational change responsible for viral cellular membrane
apposition, thereby allowing entry of the viral genetic material into the cytosol. Inhibition of these events
can be exploited to develop new drug candidates against non-trivial protein targets. To design novel
molecules for HIV-1 entry inhibition, a computational approach involving molecular docking and protein
ligand interaction studies was carried out on HIV-1 gp120 and HIV-1 gp41. Initially receptor structures were
explored for determining active site. Reported inhibitors of HIV-1 gp120 were docked into CD4 binding site
of HIV-1 gp120 and inhibitors of HIV-1 gp41 were docked into the hydrophobic pocket of CHR coiling
domain of HIV-1 gp41. Glide XP mode was used for molecular docking, all the docked conformations were
analyzed and a relation between biological activity and Emodel of complexation was obtained. Further the
best docked molecule and most potent inhibitors were re-docked into the respective binding sites using
Induced fit docking (IFD) protocol. This gave us the insight on structural requirements for binding of
inhibitors to receptor. Based on these structural features novel molecules were designed and docked into the
receptor binding site using both docking protocol. Molecules with better interactions and binding affinities
on HIV-1 gp120 were synthesized and screened for their biological activity. Novel symmetrically N, N-
disubstituted urea and thiourea were synthesized using microwave assisted synthesis under aqueous
medium. Synthesized molecules were screened for their HIV-1 gp120 CD4 binding inhibition ability by
HIV-1 gp120 CD4 capture enzyme linked immunosorbent assay. Designed molecules were found to inhibit
HIV-1 gp120 CD4 binding in micro molar concentrations. Designed molecules for gp41 with better
interactions and binding affinities will be synthesized and screened for their biological activity.
NH NH
X
L L
FHC FHC
X = O or S L = Linker
FHC = Fused Hetrocycle
Designed HIV-1 gp120-CD4 binding inhibitors









Synthesis of Novel Pyrazole derivatives: An investigation on their ability to inhibit
Monoamine Oxidase (MAO)

A. Therasa Alphonsa
a
, C. Loganathan
a
, S. Kabilan
a

a
Department of Chemistry, Annamalai University, Annamalainagar, Chidambaram, Tamilnadu-608 002,
India.


Monoamine oxidases are widely distributed enzymes that contain a avin adenine dinucleotide (FAD)
covalently bounded to a cysteine residue. Many living organisms possess MAOs and in mammals two
isoforms are present, MAO-A and MAO-B, located in the outer membrane of the mitochondria. These two
isoforms are involved in the oxidative deamination of exogenous and endogenous amines, including
neurotransmitters, thus modulating their concentrations in the brain and peripheral tissues. The MAO-A
inhibitors (MAOI-A) are used as antidepressants, while MAOI-B are used in the treatment of Parkinsons
disease.To identify the novel MAO-A inhibitors, a series of selective pyrazole derivatives were synthesized
and docked with high resolution crystal structures of MAO-A isoform. Use of docking study approaches
are leading to a better understanding of the main binding interactions of several inhibitors at the enzymes
active sites, and have facilitated the interpretation of their structureactivity relationship

















SYNTHESIS, MOLECULAR DOCKING, AND EVALUATION OF SOME NOVEL ANALOGUE
OF N'-[SUBSTITUTED] PYRIDINE-4-CARBOHYDRAZIDES AS POTENTIAL THERAPEUTIC
AGENTS

Atre, N. M.
*1
; Mandlik, P. R.
2
and Khedkar, D. D.
3

1
Department of Bioinformatics, Shri Shivaji Science College, Amravati- 444603, Maharashtra
2
Department of Chemistry, Shri Shivaji Science College, Amravati- 444603, Maharashtra
3
Department of Botany, Shri Shivaji Science College, Amravati- 444603, Maharashtra

Email: neet3atre@gmail.com

The present work aims to synthesize some novel analogue of N'-[Substituted]Pyridine-4-
Carbohydrazides. The synthesized compounds were characterized by elemental analysis, physical and
spectral data (IR, 1HNMR). Literature survey shows its antiviral, antibacterial, antitumor and anti-
carcinogenic activities. Seven synthesized analogues of N'-[substituted] pyridine-4-carbohydrazides and 30
similar drugs available in public domain database were docked against the Quinolinate
Phosphoribosyltransferase (Qaprtase) from Mycobacterium tuberculosis (PDB ID: 1QPR) active site cavity
with favorable ligand-protein molecular interaction. Calculation of molecular properties, pharmacophore
patterns and ADMET properties using Schrodinger Maestro 9.4 suite for these analogues shows enhanced
pharmacological properties similar to available drugs.
Keyword: Carbohydrazides, Molecular Docking, ADMET
















DESIGN, SYNTHESIS, DOCKING, QSAR STUDIES AND ANTICANCER EVALUATION OF SOME
NOVEL BENZAMIDE DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS

Avineesh Singh*, Harish Rajak, Vijay Patel

Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur (CG)-495 009 India.
Email: avineesh26@gmail.com

Cancer is projected to become the leading cause of death worldwide in the year 2010, according to a new
edition of the World Cancer Report from the International Agency for Research on Cancer. All newly
synthesized compounds were characterized using IR,
1
H NMR, MS and elemental analysis followed by
evaluation of their cytotoxic activity by MTT assay on HCT-15 cancer cell lines. The docking and
QSAR studies of all compounds were performed using Schrodinger Suite Software 2012 employing the
Histone Deacetylase Like Protein (HDLP) obtained at 2 A resolution (PDB ID: 1ZZ1). All the synthesized
compounds have shown varying degree of anticancer activity in the range of 8.6 to 80 g/ml. Among all
the synthesized compounds, 7S was found to be most potent with IC
50
value of 8.6 g/ml showed significant
anticancer activity against HCT-15 cancer cell lines. The docking studies indicated that the 4-
methoxyphenyl derivative exhibited lower scoring energies suggesting favorable binding of these ligands to
the protein with reference to SAHA with hydrophobic and van der Waals interactions. The hydrogen
bonding interaction between the compounds and the amino acid residues at the binding pocket of HDLP
showed that presence of hydrophobic aryl ring and the benzamide groups with free amino moiety are
important for anticancer activity. The results of the docking studies co-related well with the biological
activity. As the synthesized 4-methoxyphenyl derivative exhibited significant anticancer activity, this class
of drug can be further explored to develop more potent anticancer agents. QSAR study for all synthesized
derivatives was carried out by using maestro, phase of Schrodinger suite 2012. All derivatives showed
significant anticancer activity. QSAR result for anticancer potential produced highly predictive model that
has excellent r
2
0.91.












In silico docking analysis of GC-MS derived compounds from Emilia sonchifolia (L.) DC against
Pancreatic cancer

Pratibha Prabhakaran
1
, P. Chella Perumal
1
, D. Sophia
2
and V.K. Gopalakrishnan
1

1
Department of Bioinformatics, Karpagam University, Coimbatore, Tamil Nadu-641 021

2
Department of Biochemistry, Jyoti Nivas Degree College,Koramangala, Hosur Road, Banglore-560095



Pancreatic cancer is the tenth most commonly diagnosed disease which is increasing in India and is
the fourth leading cause of cancer death in the United States. Emilia sonchifolia (L.) DC (Asteraceae) is an
edible plant used in the Ayurvedic system of medicine. Plants serve as sources of compounds that act a
potential therapeutic agent for treatment of various diseases. The utility of these plants and its scientific
validation might have an effective tool for the development of drug discovery. On this account the present
study aimed to analyze the presence of bioactive compounds in the n-Hexane extract of Emilia sonchifolia
(L.)DC by GC-MS analysis and to validate the activity of the compounds against pancreatic cancer targets
(AKT and mesothelin) through in silico docking method. The GC-MS result has shown totally 80
compounds present in the n-Hexane extract of Emilia sonchifolia (L.) DC. These compounds were subjected
to ADME properties prediction and molecular docking studies (using QikProp and Glide in Schrodinger
suite) with ATK and Mesothelin proteins which are over expressed in the pancreatic cancer. Molecular
docking studies revealed that 1-(3-methoxy-2-pyrazinyl)-2-methyl-1-propanone exhibits the highest docking
score on both AKT and mesothelin target protein compared with FDA approved drugs and other bioactive
compounds present in the n-Hexane extract of Emilia sonchifolia (L.). This study concluded that the
bioactive compound 1-(3-methoxy-2-pyrazinyl)-2-methyl-1-propanone may act as a good inhibitor for both
AKT and mesothelin target proteins in pancreatic cancer. Thus it may lead to the development of novel drug
against pancreatic cancer.

Keywords: Emilia sonchifolia (L.) DC , GC-MS, Pancreatic cancer, ADME, Molecular docking.
















Synthesis, evaluation and molecular docking study of some new p-aminobenzoic acid derivatives as an
antiamnesic and cognition enhancing agents
Saurabh K. Sinha, Sushant K. Shrivastava
Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutics, Indian Institute of
Technology, Banaras Hindu University, Varanasi, U.P. 221005, India.

Alzheimers disease is a progressive neurodegenerative disorder, characterised by selective loss of
cholinergic neurons and accumulation of -amyloid protein in the selective brain areas such as cortex and
hippocampus.
1
Loss of memory, cognitive decline, impaired performance of activities of daily life and
behavioural changes are hallmark of Alzheimers disease.
2
Patients suffering with AD have low level of
acetylcholine (ACh) and choline acetyltransferase (ChAT) in the cortex and hippocampus. In our earlier
studies, we have reported some new schiff bases, anilide, imide and semicarbazones of 4-aminopyridine for
their cognition enhancing, antiamnesic and anticholinesterase activities among which benzophenone and
imide derivatives were found to be highly significant. In continuation of our previous research work
3-5
we
have designed and synthesized some new semicarbazones of p-aminobenzoic acid and evaluated for
antiamnesic, cognitionenhancing and anticholinesterase activities. The results illustrated a significant
cognition enhancing effect on elevated plus maze model with a significant reversal of scopolamine-induced
amnesia. A significant inhibition in acetycholinesterase (AChE) activity by all the synthesized compounds in
specific brain regions that is, prefrontal cortex, hippocampus and hypothalamus was observed. The IC
50

value and selectivity of synthesized compounds showed a comparable activity of 19 (0.0460.016 M and
11.960.64), (260) with reference standard donepezil (0.040.012 M and 15.24 0.86 M), (381) for
AChE and BChE inhibition respectively. Its enzyme kinetic study revealed a non-competitive inhibition of
AChE (Ki = 0.032 0.014) and a competitive inhibition of butyrylcholinesterase (BChE) (Ki = 8.46 0.62).
Docking studies predicted the binding modes of these compounds in AChE and BChE active sites and
showed an affinity with the key peripheral anionic site residues Trp-286, Tyr-124 and Tyr-341 of AChE and
Leu-286 and Val-288 of BChE. All the computational study confirmed their consensual interaction with
AChE and BChE justifying the experimental outcome.
1. Gil-Bea, F. J.; Garcia-Alloza, M.; Dominguez, J.; Marcos, B.; Ramirez, M. J. Neurosci. Lett.
2005, 375, 37.
2. Mohamed, T.; Rao, P. P. N. Curr. Med. Chem. 2011, 18, 4299.
3. Sinha, S. K.; Shrivastava, S. K. Med. Chem. Res. 2012, 21, 4395.
4. Sinha, S. K.; Shrivastava, S. K. Bioorg. Med. Chem. Lett. 2013, 23, 2984-2989.
5. Sinha, S. K and Shrivastava, S. K. Bioorg. Med. Chem. 2013, 21, 5451-5460.







IN-SILICO DESIGN OF NOVEL SIRT1 INHIBITORS FOR TARGETING BENIGN PROSTATIC
HYPERPLASIA
Mallika Alvala
a,$*
, Ravi Alvala
b
, Madhu Babu battu
a
, Venkat Koushik Pulla
a
, Yogeeswari Perumal
a
,
Sriram Dharmarajan
a
.
a
Birla Institute of Technology and Science, Pilani-Hyderabad Campus,
Hyderabad-500 078, AP, India.
b
G.Pulla Reddy College of Pharmacy, Mehdipatnam, Hyderabad-500 028, AP, India
$
National Institute of Pharmaceutical Education and Research, Hyderabad-500 037, A.P, India
Homology model of hSIRT1 catalytic domain was prepared using Prime, module of Schrdinger and active
site was identified by sitemap program. With the aim to design novel small molecule SIRT1 inhibitors
against benign prostatic hyperplasia, high throughput virtual screening of in house database of ~3000
molecules was performed. Benzthiazolyl-2-thiosemicarbazone scaffold has been identified as lead scaffold
with highest docking score hence, a total of 16 derivatives (BH1-16) were synthesized and characterized. In
vitro hSIRT1 activity assay revealed the significant SIRT1 enzyme inhibition by compounds BH1 and BH13
with an IC
50
of 46.270.7M and 15.30.8M respectively. MTT assay of BH1-16 on different cancer cell
lines (K562, MDA-MB 231, LNCaP and PC3) confirmed the significant growth inhibition of LNCaP cells
by BH1 (IC
50
4.09 M) and BH13 (IC
50
5.07M) with no cytotoxicity on HEK293 cells. Mechanistic studies
of BH1 and BH13 on LNCaP cells, illustrate a dose-dependent increase in annexin V positive cells and
activation of Caspase 3, demonstrating the induction of apoptosis. A dose dependent decrease in transcript
levels of SIRT1, Prostate specific antigen and increase in protein levels of p53 indicate the SIRT1 mediated
apoptosis effects of BH1 and BH13. In vivo studies on testosterone-induced benign prostate hyperplasia in
male wistar rat, BH1 and BH13 showed significant decrease in hyperplasia and SIRT1 transcript levels
compare to positive control. In conclusion, the present study demonstrates the in silico designing
corresponds to the in vitro and in vivo potential effects of Benzthiazolyl-2-thiosemicarbazone derivatives
against benign prostate hyperplasia via SIRT1 inhibition.









Identification of Aurora kinase A Selective inhibitor through Structure-Based Virtual Screening
(SBVS)
Mohane S. Coumar,
a,*
Sailu Sarvagalla,
a
Vivek Kr. Singh,
a
John Tsu-An Hsu
b
and Hsing-Pang Hsieh
b,*

a
Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014,
India

b
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan
Road, Zhunan, Miaoli County 350, Taiwan, ROC
E-mail:mohane@bicpu.edu.in, hphsieh@nhri.org.tw

Aurora kinases have emerged as promising targets for cancer therapy because of their critical role in mitosis.
These kinases are well-conserved in all eukaryotes. The activity of Aurora kinases is regulated mainly by
phosphorylation and degradation. In many of human cancers its expression is up regulated thats make an
indication that these kinases are involved in cancer regulation.
In the present study, in-house HTS library (125,000 compounds) was screened in silico using two docking
programs: Glide XP and Libdock. From each docking experiment top scoring thirteen compounds were
prioritized and tested for Aurora kinase A enzyme inhibition. Two compounds, CSV0B000620 (Aurora A
IC
50
= 341 nM, Mol.Wt = 220.2, ligand efficiency (LE) = 0.52) and CSV0C013921 (Aurora A IC
50
= 852
nM, Mol.Wt = 254.1, LE = 0.44,) showed better inhibition against Aurora Kinase A enzyme. CSV0C013921
was also identified as aurora A selective inhibitor with less than 30.9% inhibition of Aurora B enzyme at 50
uM concentration. CSV0C013921 was subjected to Glide XP docking and MM/GBSA (PRIME)
calculations. Further detailed molecular dynamics simulation helped to understand the factors involved in
the Aurora A selectivity of the compound.
N NH
O
N
N
H
N
H
2
N
O
CSV0C013921
CSV0B000620










DOCKING STUDIES OF SOME NOVEL OXAZINE SUBSTITUTED 9-ANILINO ACRIDINE
DERIVATIVES WITH TOPOISOMERASE II, SYNTHESIS AND EVALUATION FOR THEIR
ANTI-TUMOUR ACTIVITY
R. Kalirajan
1
, Niroj Shrestha
2
, S. Sankar
1
and S. Jubie
1

1
Department of Pharmaceutical Chemistry,
2
Department of Pharmacology, JSS College of Pharmacy (A
Constituent college of JSS University, Mysore), Udhagamandalam 643001, Tamil Nadu, India
E-mail: rkalirajan@ymail.com, shreniroj@gmail.com

A series of some novel oxazine substituted 9-anilinoacridines were designed for docking studies towards the
key Topoisomerase-II (1ZXM) by using Schrodinger Maestro 9.3 version. The insilico ADME screening for
the compounds were performed by qikprop module of Schrodinger software. The oxazine substituted 9-
anilino acridine derivatives 5a-f had good docking scores against topoisomerise II compared with standard.
The compounds 5a-f with good Glide score were synthesized. The synthesized compounds were
characterized and conformed by IR, NMR and Mass spectroscopy. The 3D QSAR studies for synthesized
compounds were performed by PHASE module of Schrodinger software. The compounds 5a-f were
evaluated for their anti-tumor activity against Daltons Lymphoma Ascites (DLA) cell growth by invitro
method. It was revealed that these compounds exhibited significant anti-tumor activity. All the oxazine
substituted 9-anilino acridines have more significant CTC
50
(concentration required to reduce viability by
50%) value in the range of 96-365 g/ml. There is good correlation between docking and anti-tumor
activity.















MOLECULAR DOCKING STUDY OF 4-THIAZOLDINONE DERIVATIVES AS INHIBITORS OF
HIV-RT AND VIRTUAL SCREENING


Anil kumar. N*, Priyam Thakor, B. Shivakumar, R. B. Kotnal
Department of Pharmaceutical Chemistry, BLDEAs College of Pharmacy, BLDE University campus,
Bijapur-586103, Karnataka, India


The generation of anti-HIV agents using structure-based drug design methods has yielded a number of
promising non-nucleoside inhibitors (NNIs) of HIV reverse transcriptase (RT). Recent successes in
identifying potent NNIs are reviewed with an emphasis on the recent trend of utilizing a computer model of
HIV-RT to identifying space in the NNI binding pocket that can be exploited by carefully chosen functional
group predicted to interact favourable with binding pocket residues. The NNI binding pocket model was
used to design potent NNIs against both wild-type RT and drug-resistant RT mutants. Molecular modelling
and score function were used to analyze how drugresistant mutations would change the RT binding pocket
shape, volume and chemical make-up, and how these changes could affect inhibitors binding. HIV-1(human
immunodeficiency virus type-1) is the pathogenic retrovirus and causative agent of AIDS. HIV-1 RT is one
of the key enzyme in the duplication of HIV-1. Inhibitors of HIV-1 RT are classified as NNRTIs and
NNRTIs bind to a region that is not associated with the active site of the enzyme. Within the NNRIs
category, there is a set of inhibitors commonly referred to as thiazolidinones derivatives. The present 3D-
QSAR study is an attempt to explore the structural requirement of thiazolidinones derivatives for anti-HIV
activity. Based on the structural and bio-data of previous thiazolidinone analogs, 3D-QSAR studies have
been performed with a training set consisting 500 molecules, which resulted in one reliable computational
model. It is shown that the steric and electrostatic properties predicted by in-silico drug designing and the
hydrogen bond acceptor, hydrogen bond donor and hydrophobic properties predicted and were related to
anti-HIV activity. The synthesis of 4-Thiazolidinone,3-(4-methylphentyl)-1,3-thiazolidin-4-one was carried
out by Microwave Irradiation of p-methyl aniline, Formaldehyde and thioglycolic acid. The target
compound was characterised by IR, NMR, and Mass spectral data. The compound was evaluated for anti-
inflammatory activity. The result of In-silico model and synthesised compound was compared and were
promising.









In silico design, synthesis and Antidiabetic evaluation of some novel DPP-IV inhibitors
Anjana.A.K, Sugun Kumar Sharma, Prasanth Francis, Dr.M.J.N. Chandrasekar.
Department Of Pharmaceutical chemistry, JSS College of pharmacy, Ootacamund, T.N

Amino acids can, under appropriate conditions, enhance insulin secretion from primary islet cells
and - cell lines. In periods of fasting or starvation, amino acid release from skeletal muscle (primarily L-
glutamine and L- alanine) may modulate glucagon release from pancreatic -cells, which subsequently may
influence insulin secretion from - cells. Dietary amino acids may also stimulate incretin release, e.g., GLP-
1, from intestinal L- cells and therefore stimulate insulin secretion via indirect mechanisms. The positive
effect of administration of two amino acids to insulin secretion in in vivo was reported in a recent clinical
assessment of the effect of leucine and phenyl alanine. Therefore bis amino acid peptidomimetics may prove
as a potent DPP-IV inhibitors which apart from acting as antidiabetic agents, render essential amino acids
after metabolism and directly or indirectly aid in the secretion of insulin and control the complications of
diabetes.
From four amino acids such as Glycine (Y), Alanine (Y
1
), Leucine (Y
2
), and Valine (Y
3
), some
dipeptides based on permutations and combinations along with attachment on both sides of dipeptide with
some heteroaromatic groups, were generated with a virtual library of about 300 molecules. The generated
library of 300 ligands was screened on in silico crystal structure of DPP-IV protein (PDB id- 3NOX)
obtained from protein data bank. The study was performed using glide extra precession mode of Schrdinger
software. From the obtained in silico results, best 20 ligands were shortlisted and were further subjected to
induced fit docking studies in comparison with four marketed standard drugs namely sitagliptin, vildagliptin,
saxagliptin and alogliptin. From induced fit docking studies the molecules which showed better results than
standard were selected for synthesis. The final compounds namely AGSS208, AGSS108 and AGSS109
were taken up for further in vitro DPP-IV inhibition assay using DPP-IV inhibition assay. All the three
molecules showed promising DPP-IV inhibition on in vitro studies. One of the synthesized DPP-IV inhibitor
(AGSS208) showed good in vitro antidiabetic potential.














Quinolines as anticancer agents: The probable candidates for HDAC inhibition
Aparna V. Chavan, Pooja U. Trivedi, Supriya S. Mahajan
C. U. Shah College of Pharmacy, S. N. D. T. Womens University, Juhu Tara Road, Santacruz (W),
Mumbai- 400049, India
E-mail: aparna387@yahoo.com

Aim: To design, synthesize and evaluate the anticancer potential of 4-amino-7-chloroquinolines.
Objective: Quinolines exhibit a variety of biological activities like antimalarial, anticancer, anti-tubercular,
etc. Extensive literature search shows that anticancer nature of quinolines is because of HDAC inhibition.
Hence, the objective of this study is to design, synthesize and evaluate 4-amino-7-chloroquinolines as
anticancer agents.
Experimental:
Designing of 4-amino-7-chloroquinolines: In silico drug designing and docking approach saves time and
money. Docking predicts the affinity of ligands for the target. Docking study was carried out by using the
software Glide from Maestro 9.3 of Schrdinger, USA.
HDAC inhibition: Flexible docking (Figure 1) was done on HDAC enzyme (PDB ID 1T69) using SP mode
and was compared with suberoylanilide hydroxamic acid (SAHA). Hundreds of 4-amino-7-
chloroquinolines were screened and few selected compounds were synthesized on the basis of G-score,
hydrogen bonds and Vdw interactions.
Synthetic Methodology: N-(Aminoalkyl)-4-amino-7-chloroquinolines and N-(aminophenyl)-4-amino-7-
chloroquinolines were synthesized on laboratory scale from 4, 7-dichloroquinoline. Various substituted
amides, amines, sulfonamides and dithiocarbamic acid alkyl esters were synthesized. Their structures were
characterized and confirmed by IR and
1
H-NMR spectroscopy, respectively.
Pharmacological evaluation: Acute oral toxicity studies were carried out as per the OECD 423 guidelines.
Anticancer activity was evaluated by SRB assay using MCF7 cancer cell line. Results & discussion:
Results of anticancer activity are encouraging. G-scores of the compounds were well correlated with their
anticancer activity. Thus, 4-amino-7-chloroquinolines can be a new class of anticancer compounds.










Design and Synthesis of new class of ErbB2 inhibitors 4-thiazolidinones by one pot
approach.
Ananda.H, K.S. Sharath Kumar, Harsha K.B, K. S. Rangappa
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-06, India

The cancer chemotherapy has entered a new arena of molecular targeted therapeutics. The ErbB2
(also known as HER-2) receptor is a proto-oncogene associated with a poor prognosis in breast cancer.
Herceptin, the only humanized anti-ErbB2 antibody currently in clinical use, has proven to be an essential
tool in the immunotherapy of breast carcinoma, we have synthesized ErbB2 inhibitors using 4-
thiazolidinones which represent an important class of heterocyclic compounds because of its diverse
biological activities. We herein report Propylphosphonic anhydride (T3P

)-DMSO mediated oxidation of

alcohols to carbonyl compounds and their subsequent cyclization with aryl/hetero aryl amines and
thioglycolic acid to afford 4-thiazolidinones. Synthesis of 4-thiazolidinones directly from alcohols has been
carried out for the first time. Mild reaction conditions, wide functional group tolerance, ease of workup and
good yields are the noteworthy features of this protocol. Docking studies were performed into the ErbB2
active site to determine the probable binding pattern. Antiproliferative assay results indicating that some of
the thiazolidinone derivatives own high antiproliferative activity against MCF-7. Compounds that inhibit the
kinase activity of ErbB2 after binding of its cognate ligand are of potential interest as anticancer agent
deserves future research.







Synthesis of novel benzoxazine-based aglycones that targets glycosidases and sodium/glucose
cotransporter 1

Bharathkumar H,
1
Shanmuga Sundaram M,
2
Jagadeesh Das,
3
, Shardul Paricharak,
4,5
Anusha Sebastin,
1

Babu Rajeev,
1
Srinivas V,
1
Rangappa K.S,
3
Adriaan IJzerman,
5
Kemparaju K,
2
Girish KS,
2
Andreas
Bender,
4
and Basappa
1


1
Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Palace Road,
Bangalore-560001, India;
2
Department of Studies in Biochemistry, University of Mysore, Mysore 570006,
India;
3
Department of Chemistry, University of Mysore, Manasgangotri, Mysore-560001, India;
4
Unilever
Centre for Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2
1EW, Cambridge, United Kingdom, and
5
Division of Medicinal Chemistry, Leiden/Amsterdam Center for
Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Glycoside hydrolases catalyze the selective hydrolysis of glycosidic bonds in oligosaccharides,
polysaccharides, and their conjugates. -glucosidases occur in all domains of living organisms and
constitute a major group among glycoside hydrolases. On the other hand, the benzoxazinoids occur in living
system and acts as stable -glucosides namely, 2-(2,4-dihydroxy-7-methoxy-2H- 1,4-benzoxazin-3(4H)-
one)--D-gluco-pyranose. Here, we synthesized the aglycones by using the chloro acetic acid catalytic
system to the aerobic oxidative synthesis technology to develop novel heterocycles like 1,3-benzoxazines
efficiently from the one-pot reaction of aldehydes with 2-aminobenzyl alcohols. These benzoxazines
structurally mimic the naturally occurring aglycons like MBOA (6-methoxybenzo[d]oxazol-2(3H)-one,
BOA (benzo[d]oxazol-2(3H)-one). These benzoxazines [3-(2,4-dihydro-1H-benzo[d][1,3]oxazin-2-yl)-4H-
chromen-4-one (HDA-36), 4-(2,4-dihydro-1H-benzo[d][1,3]oxazin-2-yl)phenol (HDA-37), 4-(7-chloro-2,4-
dihydro-1H-benzo[d][1,3]oxazin-2-yl)phenol (HDA-38) shows inhibitory activity towards glucosidase is
significant when compared to acarbosetetrasaccharide with a IC
50
Values (g/ml) of 4.0, 3.9 and 3.5
respectively. Based on the target prediction tool (NB classifier) results these aglycones (benzoxazines)
potentially target the sodium/glucose co transporter1 with a score of 2.70. The in vitro glycosidic activity
was correlated with the in silico docking correlations with a high docking score for the HDA-38 towards the
aglycones binding site of glycosidase. In addition, the in vitro and in vivo anti-hyperglycemic effect of
HAD-38 significantly reduced the plasma glucose concentration of the mouse treated with maltose as
substrate when compared to maltose control group.








Structural Insights to Target Epidermal Growth Factor Receptors Dimerization with Novel Small-
Molecule Inhibitors
APPAJI DOKALA
Department of Pharmaceutical Chemistry, Vishnu Institute of Pharmaceutical Education and Research,
Narsapur-502313, Medak

The epidermal growth factor (EGF) receptor is a receptor tyrosine kinase involved in the control of cell
proliferation. EGF receptor dimerization is a pre-requisite for kinase activation, and is the basis for
exploring the feasibility of inhibiting EGF receptor activation by blocking dimer formation with small
molecules. A compound 32, initially identified by virtual screening, was shown experimentally to inhibit
EGF receptor kinase activation in a dose-dependent manner. This compound blocked EGF-stimulated dimer
formation as measured by chemical cross-linking and luciferase fragment complementation. This first-
generation lead compound represents the best small-molecule inhibitor of EGF receptor activation that is not
directed against the intracellular kinase domain.


























Synthesis, Molecular docking, ADMET studies and Cytotoxic screening of Some Novel Nitrogen
Bridge head Heterocycles Containing 1,2,4-Triazolo[3,4-B](1,3,4)-Thiadiazole Moiety
Bincy B.C*, Jubie.S, Naga Srinivas T, Ashish Wadhwani
1
, Patel Viral
1
and Md.Afzal Azam
Department of Pharmaceutical Chemistry
1
Department of Pharmaceutical Biotechnology, JSS College of
Pharmacy, (Off Campus-JSS University, Mysore), Udhagamandalam, India-643001

A series of novel nitrogen bridge head heterocycles containing 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole moiety
(1a-e) and (2a-e) were synthesized in successful yield, by cyclocondensation of 4-amino-5-substituted-
(1,2,4)-triazolo-3-thiol with different substituted aromatic aldehydes in presence of potassium carbonate. To
investigate their anticancer activity on the structural basis, in-silico molecular docking studies have been
carried out. All the compounds were docked towards the enzymes human fatty acid synthase thioesterase
domain [PDB ID: 2PX6] by GLIDE integrated maestro (9.3 version). The compounds 1c, 1d, 1e, 2b, 2e
showed comparable results when compared to the known human fatty acid synthase thioesterase domain
inhibitor orlistat. Also, they exhibited desirable ADMET properties. Further the compounds have screened
for their in-vitro cytotoxicity towards MCF cell lines by SRB method. It has been observed that there is a
significant correlation between in-silico and in-vitro studies.
Key words: triazolothiadiazole,cytotoxicity,in silico,human fatty acid synthase, ADMET.











Design, Synthesis and Biological Evaluation of 6, 7-Dimethoxy-N-
Phenylquinazolin-4-Amine derivatives as Potent CLK1 Inhibitors
Digambar Kumar Waiker
a
, C. Karthikeyan
a
, Olivier Lozach
b
, Laurent Meijer
b
. Prof. Piyush Trivedi
a

School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport road Bhopal,
Madhya Pradesh-462033
Protein Phosphorylation and Human Disease Group, USR3151, Station Biologique, B.P. 74, 29682 Roscoff
Cedex, Bretagne, France

CLK1 was one of the first dual specificity kinases discovered. CDC-like kinase (CLK) is a protein kinase
with dual specificity; it can phosphorylate both serine/threonine and tyrosine residues. Quinazoline is the
most promising scaffold for drug discovery efforts targeted towards kinases. 6, 7-dimethoxy-N-
phenylquinazolin-4-amine derivatives (DW-01 to DW-10) were designed, synthesized and evaluated for
kinase inhibitory activity against five kinases implicated in neurodegeneration (CLK1, DYRK1, GSK 3 ,
CDK5, CK1). Compound DW-05 was identified as a highly potent inhibitor of the CLK1 (IC50=1.5M) and
GSK3 , (IC50=3M). Docking studies suggested that substituted 6, 7-dimethoxy-N-phenylquinazolin-4-
amine bind to the ATP-binding site of the both enzymes deriving their affinity mainly by interactions with
apolar side chains of the ATP-binding pocket as well as by formation of specific hydrogen bonds with the
amino acid residues in the hinge region of kinase.











A newer outlook to cardiac arrhythmia: Lead development by targeting Calsequestrin and its calcium
binding
Harapriya Chakravarty,
1
Amit Kumar,
2
Naresh C. Bal,
3
Chandralata Bal,
1
Ashoke Sharon
1

1
Department of Applied Chemistry, Birla Institute of Technology, Mesra, Ranchi, Jharkhand-835215, India.
CRS4, Bioengineering group, Science and Technology Park Polaris, Piscina Manna, Italy
3
Department of
Physiology and Cell Biology, The Ohio State University,College of Medicine, Columbus, OH 43210

Cardiac dysrhythmia (which is also known as arrhythmia or irregular heartbeat) is any of a large and
heterogeneous group of conditions which is due to abnormal electrical activity in the heart and very often
has an extremely high unpredictability and noxious consequence. Arrhythmias are complex health issues
affecting many people worldwide. Research over the years has established that these conditions arise due to
altered Ca2+-handling, although exact molecular details are still under investigation. Various mutations in
calsequestrin, lead to fatal cardiac arrhythmias called Catecholaminergic polymorphic ventricular
tachycardia. In order to understand how a molecule could modulate its polymerization our first approach
was to understand its calcium binding with its polymerization. Our present work is on the determination of
the structure of calsequestrin using Prime for Homology modeling, Loop refinement followed by Molecular
dynamics simulation to envision its calcium binding properties. The molecular dynamics simulation at
various calcium concentrations showed how the C-terminal, which is missing in the crystal structure, adopts
a favorable orientation with an increase in calcium concentration. Moreover understanding of specific
calcium binding sites shows us the ways that which of these sites are more likely to buffer calcium. Since
there is no reported binding site for binding of calsequestrin modulator, we used Site map for the
determination of ligand binding sites, the possible lead molecules were docked to find a favorable
interaction with the protein inhibiting the N-terminal insertion and disrupting the polymerization.
The preliminary designed molecules were synthesized and biological studies provided significant results as
possible polymerization inhibitor. Thus, the further lead optimization and biological studies are in progress,
which could have a significant role as an anti
arrhythmic agent. (Acknowledgement:
Department of Biotechnology, Government of
India for Financial Support)

Fig1-Synthesized molecule interacting at the
interface of two chains
















\

Structure guided designing of potential lead motifs against Cancer

Arun Kumar V.A
1
, Keshav Mohan
2

1
Department of S & H (Computer Applications), Sathyabama University, Chennai. India
2
SVN College f Engineering, Mavelikkara, Kerala , India. Corresponding Author
1

E-mail:akva1234@yahoo.com

On the basis of stereo specific information obtained from the crystal structures of CDK2, indole and
chromene analogues were designed by suitably substituting the pharmacophores on their moiety and docked
with target protein for calculating binding affinities. The binding affinities were represented in glide score.
(5E)-5-[(1-methyl-1H-indol-3-yl)methylidene]-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I
1
), (5E)-5-(1H-
indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I
2
) and 2-amino-4-(4-methyl phenyl)-5-
oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C
9
)were selected for synthesis and biological testing
based on vital interactions. Compounds I
2
and C
9
were proved to be active against MCF-7 and HeLa cell
lines.
Keywords: CDK, pharmacophores, MCF-7, HeLa.









Identification of Potential Inhibitors for Regulating Keap1-Nrf2 Function

Prashant Deshmukh, Lata Chaunsali, Manjula Ramu and Balasundaram Padmanabhan
Department of Biophysics, National Institute of Mental Health and Neuroscience, Bangalore 560 029, India.

Neurodegeneration in humans is known to occur as a result of several primary causes, including expression
of certain gene alleles, toxicant administration, and aging. Oxidative damage/stress (OS) has been associated
with various neurodegenerative diseases (ND) including Parkinsons disease, amyotrophic lateral sclerosis
(ALS), and Alzheimers disease, as well as non-neurodegenerative conditions such as cancer and heart.
Clinical trials are being conducted to establish the potential of antioxidant therapeutics; however, to date, no
drugs are available in the market.
The activation of Nrf2/ARE in the Phase II defence system regulates the expression of antioxidant
enzymes. Under unstressed conditions, Nrf2 binds to Kelch-like ECH-associated protein 1 (Keap1) and
undergoes constitutive proteasome-dependent degradation. In the presence of OS, Keap1 changes its
conformation and releases Nrf2, which translocate into the nucleus and binds to ARE; thereby activate
several cytoprotective genes. The expression and/or activation of Nrf2 in neurons can be strongly protective,
and thus the Nrf2 system is a potential drug target in neurodegenerative diseases.
In this context, we have been working on the Keap1-Nrf2 system to discover potential inhibitor
compounds for Nrf2 activation, by rational drug discovery approach. We present here new hits of Keap1
inhibitors, obtained by in-silico method, and confirmed by preliminary fluorescent-based binding studies.











Structure based docking assisted identification of 4-(benzylidene)hydrazinothazoles as novel aurora
kinase inhibitors
Sarah T., Sreejalekshmi K. G
*
Department of Chemistry, Indian Institute of Space Science and Technology, Thiruvananthapuram, Kerala,
695 547, India
E-mail:Sarah.11@iist.ac.in

Anti-cancer drug development, despite the huge investment and extensive research, is yet to
conquer many challenges including selective targeting and high specificity of drugs. The availability of huge
number of potential lead molecules as well as targets for anti-cancer drug development make the discovery
and development process further more complex where the right combination of activity, specificity, stability
and safety studies on a selected candidate is a long term and expensive research. With the advent of
powerful and accurate computational tools, researchers currently exploit molecular docking to predict the
ligand-target site interactions which ultimately take a leading role in identifying candidate targets for anti-
cancer therapy as well as assist in the discovery and optimization of novel anti-cancer agents.

Aurora kinases, one of the key regulators of mitosis, frequently over expressed in human
cancers are among recently identified targets for anti-cancer agents. Aberrant expression of these kinases
leads to chromosomal instability and derangement of multiple tumor suppressor and onco-protein regulated
pathways. Preclinical studies and phase I and II clinical trials of multiple aurora kinase inhibitors as targeted
anticancer drugs, most of them belonging to the family of heterocycles, have also provided encouraging
results.

Our longstanding interest in the design of synthetic routes to pharmaceutically relevant
heterocyclic systems, their chemical synthesis and biological evaluation have identified aminothiazole
derivatives as potential anti-cancer agents. Currently our research focus is on 4-hydrazinothiazole
derivatives. In the present work, virtual screening and molecular docking of novel 4-
(benzylidenehydrazino)thiazole derivatives as aurora kinase inhibitors and the biological evaluation of their
potential as anticancer agents is discussed.






















Combination therapy of 3, 3-Diindolylmethane and 5-Fluorouracil enhances anticancer activity in
human cervical cancer (HeLa) cell line by inducing apoptosis.
V.L.Maruthanila and S.Mirunalini*
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University,
Annamalainagar 608 002, Tamilnadu, India
E.mail: mirunasankar@ gmail.com.

Combination therapy is the most effective treatment strategy in cancer to overcome drug toxicity and drug
induced resistance. The preliminary aim of the present study was to investigate the combined treatment of 3,
3-diindolylmethane (DIM) and 5-fluorouracil (5-FU) against human cervical cancer (HeLa) cell line. The
HeLa cancer cells were treated with varying concentrations of DIM and 5-FU. Cytotoxicity of experimental
drugs was tested using MTT assay to find IC
50
value. Isobolographic method was used to calculate
combination index (CI) values from cell viability data. More over the apoptotic morphological changes have
been measured by AO-EtBr staining and DNA fragmentation CI analysis, respectively. Both DIM and 5-FU
exhibited time and concentration dependent inhibition of HeLa cell proliferation. In cytotoxicity assay the
concentration in which 50% of cell death (IC
50
value) for DIM, 5-FU and in combination of DIM with 5-FU
respectively and hence for further experiment we were chosen these concentrations. Apoptotic
morphological changes and DNA damage were observed more in DIM with 5-FU (combination therapy)
when compared to individual treatment. More over the CI value was found to be (0.36) suggested that more
synergistic effect of DIM and 5-FU against HeLa cells. Our result suggest that DIM in combination with 5-
FU could overcome the drawback of 5-FU therapy while capitalizing on the positive effects of this proven
therapy. Hence developing DIM and 5-FU a potential combinational therapy against various types of
malignancy will be promising in the future.
Keywords: HeLa cell line, DIM, 5-fluorouracil, apoptosis, cytotoxicity, combination therapy.











Pharmacophore Modeling, QSAR
and Chemoinformatics












From Natural Product To Natural Product: A Staphylococcus Aureus NorA Efflux Pump Inhibitors
Chintamani S. Jadhav*
'SI2 Unit for 2esearch an% Deve(opment of Information &ro%ucts @<opasana@, A!B+, &au% 2oa%, -othru% &une 9
$++#"A. In%ia, Email: chintamani.jadhav@urdip.res.in


Staphylococcus aureus norA gene encodes a membrane-associated protein i.e. NorA efflux pump, that mediates active
efflux of fluoroquinolones from cells. The current published medical report shows that S. aureus produces resistance
to vancomycine and ciprofloxacin which is a drug of last resort for this infection.
The inhibition of NorA efflux pump reverses the resistance caused by these pump to antibiotics. Till date there is no
report for crystallographic structure of NorA efflux protein that motivates us to develop a pharmacophore model for
this target. Phase provide excellent methodology for perceiving common pharmacophore hypothesis which give rough
idea about binding conformation of active set molecules at binding site, when there is unavailability of x-ray
crystallographic structure of target protein.
In this study a phase based common pharmacophore was developed using structurally diverse natural product reported
in literature for their NorA efflux pump inhibition. Twenty potent natural products reported from literature were
selected as active set compound. Thirty compound (20 natural products and 10 synthetic products) set were also
selected from literature which shows very less activity for NorA inhibition as inactive set.
The pharmacophore developed in this study was utilised for the screening against in-house natural bioactive database
and zinc natural product database. The 3 dimensional arrangements of pharmacophoric features and the functional
moieties identified as the optimum binding substituents into the active site of the target will be presented. These
groups will be further explored for structure activity relationship and the natural scaffolds can be considered for
development of selective NorA efflux pump inhibitors.







A Novel Strategy involving Combined Ligand and Fragment-based e-Pharmacophores to Identify
Novel and Potent RIPK1 Inhibitors

Fayaz S.M. and Rajanikant G.K.

School of Biotechnology, National Institute of Technology Calicut (NITC), Calicut, Kerala 673601.
(fayazbioinfo@gmail.com)


Receptor Interacting Protein Kinase 1 (RIPK1) is an important protein involved in Necroptosis pathway that
leads to cell death during various pathologies such as Ischemic Stroke. RIPK1 has been implied as a major
therapeutic target in necroptosis mediated cell death. Currently, Necrostatins and their analogues are the
only known inhibitors for this protein. Existing energetically optimized structure-based pharmacophore (e-
Pharmacophore) approaches involve either of the ligand-based or fragment-based pharmacophores for
virtual screening of the compounds. In this poster, a combination of ligand and fragment-based e-
Pharmacophores were derived from the protein complexes of RIPK1 in PDB. This strategy would help to
explore all the available pharmacophoric features in the binding site of the protein and would further help in
identifying novel and more potent inhibitors, with pharmacophoric features different from the existing
inhibitors. This combined e-Pharmacophore was employed for High-Throughput Virtual Screening of lead-
like compounds. Docking studies were carried out on the resulting hits and they revealed that the
compounds bind to RIPK1 with varied pharmacophoric features and good binding efficacy, compared to the
known inhibitors. Thus, this strategy can be used for any protein to identify novel and potent inhibitors.














Pharmacophore modeling, molecular docking and density functional theory
approaches for identification of novel Kinesinlike protein 1 (KIF11) inhibitor
Subramanian Karunagaran, Chandrasekaran Meganathan*
G.K.M College of Engineering and Technology, New perungulathur, Chennai 600 063, Email id:
megac2005@gmail.com

Kinesinlike protein 1 (KIF11) is a cytoskeletal motor protein that is critical to establish bipolar
spindles. Removal of KIF11 prevents centrosome migration and causes cell arrest in mitosis. KIF11 defects
are linked to the disease of microcelapathy, lymph edema or mental retardation. Pharmacophore modeling,
molecular docking and Density functional theory approaches was employed to reveal the structural,
chemical and electronic features essential for the development of small molecule inhibitor as KIF11. The
qualitative top ten pharmacophore models were developed to identify the common features. The best
pharmacophore hypothesis (Hypo1) consisting of four chemical features (two hydrogen bond acceptor ,
one hydrophobic and one ring aromatic) has exhibited high correlation co-efficient of 0.9521, cost difference
of 70.63 bit and low RMS value of 0.9475. This Hypo1 was cross validated by CatScramble method; test set
and decoy set to prove its robustness and statistical significance. Subsequently, validated Hypo1 was used
in the screening of chemical databases like NCI and Maybridge. The hit compounds were subjected to
various scrupulous druglike filters such as Lipinskis rule of five and ADMET (absorption, distribution,
metabolism, excretion, and toxicity) properties. The hit compounds were subjected to molecular docking
studies by comparing the conformation, position, and orientation (the pose) of receptor -ligand complexes as
obtained. Finally the lead compounds were subjected to DFT analysis, frontier orbitals HOMO and LUMO
clearly indicates an important role of charge-transfer interactions with the binding site in the receptor for
potent activity. The results from pharmacophore modeling, molecular docking and DFT approaches were
complementary to each other and could serve as a powerful tool for the discovery of potent small molecule
inhibitor as KIF11 agonists.
Keywords: Kinesin like protein1, Pharmacophore modeling, molecular docking and Density functional
theory.










Systematic investigation of cathepsin inhibitors using e-pharmacophore modelling A
structure based approach using energetic analysis


Mahesh Chhabria, Kailash Parmar

L. M. College of Pharmacy, Department of Pharmaceutical Chemistry,
Ahmedabad-380009, Gujarat, India


Lysosomal cysteine proteases also known as cathepsin have been recognized as potential drug targets for various
diseases such as osteoporosis, rheumatoid arthritis, cancer etc. Total 11 members of this family are known to be
expressed in the human genome, of which cathepsin K and S selectively expressed in cells capable of effectively
degrade extracellular matrix protein and in the cells of immune system, respectively. Vital role of cathepsin K
highlighted in bone resorption disease and cathepsin S, L targeted for inflammatory disease and cancer. Most
inhibitors investigated till date is known to form covalent bond to the target and only few inhibitors found to be non-
covalent. In present work we attempted to systematically analyse crystal structures of cathepsin K, S and L with bound
covalent inhibitors having better efficiency to derive energy optimized pharmacophore hypothesis. Protein-ligand
energetic terms computed using Glide XP scoring function to locate the key pharmacophore features. Energetically
favorable pharmacophore sites were used for database screening and further molecular docking study. The structural
insights obtained by this study can be used for structure based design to find novel inhibitors.
















Comparative residue interaction analysis (CoRIA): A 3D-QSAR study to inspect the
thermodynamic events involved in the binding of Trypanosoma brucei Trypanothione
reductase inhibitors

Mahesh R. Borkar, Raghuvir R. S. Pissurlenkar and Evans C. Coutinho
Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina,
Santacruz (E) Mumbai 400098, India
E-mail:evans@bcpindia.org



The Human African Trypanosomiasis (HAT) or so called sleeping sickness is a neglected tropical disease
caused by the protozoan parasites Trypanosoma brucei (T. brucei ) gambiense and T.brucei rhodesiense,
transmitted to the human (host) by the bite of the tsetse fly. HAT persists as a public health problem in
several sub-Saharan countries and affects 70 million people. The current treatment does not fulfill the need
to treat HAT because of high cost, resistance and toxicity which calls for the identification and development
of novel antitrypanosomal agents. The design of efficacious and safe drugs is expected from inhibition of
metabolic pathways that are unique and essential to the parasite and absent in the host. In this context,
Trypanothione reductase (TryR) a NADPH-dependent disulfide oxidoreductase, which is responsible for
reducing trypanothione disulfide (T[S]2) to dihydro-trypanothione (T[SH]2), is a genetically validated drug
target in the parasite T. brucei ; this is absent in human. In the present work, in house receptor-based 3D-
quantitative structure activity relationships (QSAR) methods, i.e. comparative residue interaction analysis
(CoRIA) was applied to explore the events involved in ligand binding. In this methodology, the non-bonded
interaction energies like van der Waals and Coulombic interactions of the inhibitors with the active site
residues of T. brucei TryR enzyme were calculated along with other thermodynamic descriptors and
subsequently correlated with biological activity using chemo metric methods. The major advantage of this
technique is that it can quantitatively extract crucial residues and identify the nature of interactions between
the ligand and receptor that improve the activity. In addition, other 3D-QSAR methods like CoMFA,
CoMSIA and PHASE were used to consensually analyze the models. The developed 3D QSAR models were
validated both internally as well as externally and found to be robust r
2
, q
2
and r
prcd
2
values.
References:
1. Fairlamb, A. H.; Cerami, A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu.
Rev. Microbiol. 1992, 46, 695729.
2. Patterson, S.; Alphey, M.S; et al Dihydroquinazolines as a novel class of Trypanosoma brucei
Trypanothione reductase inhibitors: Discovery, synthesis, and characterization of their binding mode
by protein crystallography. J. Med. Chem. 2011, 54, 65146530.
3. Datar, P.A.; Khedkar, S.A.; Malde, A.K; Coutinho, E.C. Comparative residue interaction analysis
(CoRIA): a 3D-QSAR approach to explore the binding contributions of active site residues with
ligands. J. Comput. Aided Mol. Des. 2006, 20, 343360.







3D-QSAR, Docking and Pharmacophore modeling of sulfamates as
human Carbonic Anhydrase II (hCA II) inhibitors

Mohit Jaiswal*, Hindol Sarkar, Saurabh M. Verma, Kalyan K. Sethi
Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi-835215, India





Three dimensional quantitative structure activity relationship (3D-QSAR) analysis was performed in order to provide
insight into the inhibitory mechanism and designing of more potent ligands using a dataset of 38 molecules consisting of
uredio-substituted sulfamate derivatives as hCA II inhibitors. Comparative molecular field analysis (CoMFA) and
Comparative molecular similarity index analysis (CoMSIA) models have been derived considering their inhibition constants
(K
i
), drafted in the range 9.9-140 nM. The ligand-based model gave q
2
values 0.736 and 0.829 and r
2
values 0.998 and 0.993
for CoMFA and CoMSIA, respectively. The predicted r
2
values are 0.564 and 0.553 for CoMFA and CoMSIA respectively.
Docking performed with the help of GLIDE (XP) on the co-crystallized protein (PDB: 1ZFQ) for the dataset molecules
gave a very decent RMSD (R
2
) value of 0.0715. Further pharmacophore model was developed by means of PHASE module
of Schrodinger which revealed that the two hydrogen-bond acceptors, two hydrogen-bond donors, and one hydrophobic
aromatic ring (AADDR) are crucial molecular features that predict binding-affinity of the ligands to the hCA II isozyme.
The r
2
and the Q
2
(r
2
pred
)

value of the best developed hypotheses is 0.8273 and 0.5233 respectively. These information
rendered by 3D-QSAR models, the docking interactions and pharmacophore modeling provide guidelines for the
development of improved hCA II inhibitors as leads for various types of disorders, such as, epilepsy, bone
resorption/osteoporosis, calcification, glaucoma and tumorigenesis.

Keywords: carbonic anhydrase II inhibitors (hCA II); uredio-substituted sulfamates; 3D-QSAR; CoMFA; CoMSIA; docking; pharmacophore
modeling















COMPUTER AIDED DRUG DESIGNING OF DUAL INHIBITORS OF
AROMATASE (CYP19) AND ALDOSTERONE SYNTHASE (CYP11B2) FOR
TREATMENT OF BREAST CANCER


Joshi Harshal, Patel Bhumika, Ghate Manjunath

Department of medicinal Chemistry, Institute of Pharmacy, Nirma University, SarkheL @andhinagar /igh9ay,
"hmeda8ad 'O2 4O?, .ndia.


The application of aromatase (CYP19) inhibitors to postmenopausal breast cancer patients
increases the risk of cardiovascular diseases (CVD), which is believed to be caused by
inhibition of estrogen biosynthesis in peripheral tissue by administering aromatase inhibitors.
Estrogen deficiency results in significantly elevated aldosterone levels, so designing Dual
inhibitors of aromatase (CYP19) and aldosterone synthase (CYP11B2) are therefore
proposed as a novel strategy for the adjuvant therapy to reduce the CVD risk for CVD
patients. Lina Yin et al
[1]
proposed such a series of pyridinylmethyl substituted 1, 2, 5, 6-
tetrahydro-pyrrolo[3, 2, 1-ij] quinolin-4-ones compounds. Qingzhong Hu et al
[2]
also
designed such series of 7-alkoxy-1-methyl-6-(pyridin-3-yl)-3, 4-dihydroquinolin-2(1H)-one
compounds for dual activity. Selected active molecules from these articles were used for
generation of pharmacophore models using phase module. Scoring of different hypothesis
for this pharmacophore model was done and based on their result, 3D-QSAR was generated.
The results obtained from 3D-QSAR showed that r
2
and q
2
values were found to be 0.7216
and 0.667 respectively. Using this data virtual screening will be done and hits will be further
considered for docking studies. Based on this result we can conclude that further synthesis of
this compounds can be carried out which will act as both aromatase as well as aldosterone
synthase inhibitors.

Keywords: - Aromatase inhibitors, Aldosterone synthase inhibitors, Pharmacophore, 3D-
QSAR, Virtual screening, Docking











Comparative genomics of aeruginosins from Microcystis aeruginosa and Pseudomonas aeruginosa:
Insights from T-cell epitope mapping, 3D-QSAR and docking perspectives with matrix
metalloproteinases.


Paramasivan Manivannan and Gangatharan Muralitharan
*


Department of Microbiology, Bharathidasan University, Tiruchirappalli-620024, Tamilnadu, India.
*
Corresponding Author drgm@bdu.ac.in


Immunomics era in the recent years has witnessed significant development in drug discovery and
immunogenic profiling. Mapping of T-cell epitopes is crucial for vaccine development. Cyanobacterial
metabolites are given importance for their diverse pharmaceutical potentials. Especially of prime importance
are oligopeptides from the Cyanobacterium Microcystis aeruginosa. Pseudomonas aeruginosa is a harmful
pathogen causing a variety of diseases ranging from Urinary tract infection to cystic fibrosis. The presence
of aeruginosins in both the bacteria have been documented for bioactivity in the cyanobacterium whereas as
a virulence factor for Pseudomonas aeruginosa. Hence a comprehensive immunome analysis has not been
studied and documented earlier. In the present study, aeruginosins from both the bacterium are chosen for T
cell epitiope mapping, 3D-QSAR and docking with matrix metalloproteinases would prove the efficiency of
cyanobacterium as potent anti inflammatory metabolite in arresting Psuedomonas aeruginosa.


Keywords
Aeruginosins, Microcystis aeruginosa, Pseudomonas aeruginosa, Immunome analysis, 3D-QSAR, Matrix
metalloproteinases












3D QSAR Study for the development of novel antiretroviral agents targeting
the protease enzymes

N.S. Kotharkar
a
, G. R. Pathade
a
S. R. Bembalkar
b
,
a.
Department Of Biotechnology Fergusson College Pune

b
. Department of Chemistry Deogiri College Aurangabad


Current targets for antiretroviral therapy (ART) include the viral enzymes reverse transcriptase and protease.
The use of a combination of inhibitors targeting these enzymes can reduce viral load for a prolonged period
and delay disease progression. However, complications of ART, including the emergence of viruses resistant
to current drugs, are driving the development of new antiretroviral agents targeting not only the reverse
transcriptase and protease enzymes but novel targets as well. In our study we have performed, Homology
modelling for Protease using SPDBV. The molecular cavities were identified using SPDBV, which shows
two potential active sites. Then Molecular modelling was performed for the protease inhibitor drugs
(Agenerase, Aptivus and Invirase). The Protein Ligand interaction was examined using Schrodinger2013-1
Software, were Agenerase shows high binding affinity, and low free energy to all the active site amino acids.
So Agenerase can be effectively used to inhibit the action of Protease, thereby inactivating the viral
replication. The results demonstrate that investigational compounds in which protease is blocked, displays
strong activity, low toxicity and excellent bioavailability, making them suitable for further exploration.
Further the ADMET property, the pharmacophore analysis and activity has to be performed for the ligands
to get a potential drug for HIV.







3D-QSAR study on PA-824 derivatives as anti-tubercular agents by Comparative Molecular
Similarity Indices Analysis (CoMSIA)

Neenu Ganesh*, Bharathkumar Inturi
,
Gurubasavaraj V Pujar
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysore-570015,
Karnataka, India.


Tuberculosis, caused by Mycobacterium tuberculosis, is of increasing concern due to the recent
emergence and spread of multidrug-resistant strains. Recently, there has been an intensive effort seeking
drugs that hit new targets, or work in new ways, since these have the potential to overcome multidrug
resistance. An exciting development has been the discovery of the 2-nitroimidazo-[2,1-b][1,3]oxazines,
exemplified by PA-824. The present work is focused on 3D-QSAR CoMSIA study for the biphenyl analogs
of the PA-824. The antitubercular activity data of the compounds for the study was collected from literature
(William A. Denny et al., 2010) and converted into -logMIC (pMIC) values for convenience. Analyses
resulted in a reliable computational model with the parameters of n= 115, r
2
= 0.712, q
2
= 0.613, SE = 0.334,
F= 102.572. The predictive ability of the resultant model was evaluated using a test set comprised of 29
molecules and the results show that the CoMFA model is able to correctly predict the antitubercular activity
of the compounds in the testing set. This model is a significant guide to trace the features that really matter
especially with respect to the design of novel potent antitubercular PA-824 analogs.

Key Words: Tuberculosis, CoMSIA, PA-824

'tructural e4ploration of car)o4amides as 55,6 antagonists (aving potent anti-!I&-.
activity )y validated comparative c(emometric tools

/ilan7an 1d(ikari8 5(anc(al Mondal8 1mit Kumar !alder and 9arun :(a
$

Natural Science Laoratory! "i#ision of $edicinal and Pharmaceutical Chemistry! "e%artment of
Pharmaceutical &echnolo'y! P.(. Bo) *+,-,! .ada#%ur /ni#ersity! Kolkata +,,,0-! India! e3mail:
nilanLanNLuphar@redi77mail.com

*espite the lo9 cost o7 highly acti,e antiretro,iral therapy, resistance to the a,aila8le drugs is a maLor
pro8lem in ".*S. )iral chemokines may 8e a lucrati,e target 7or anti3".*S therapy. .mproper expression
o7 chemokines 9as o8ser,ed in retro,irus in7ection. #P receptor 7uses the /.) en,elope glycoprotein
9ith the host cell mem8rane leading to ,iral entry into cell. /ence, no,el selecti,e #P antagonists
9ith less toxicity and resistance are pre7era8le. omparati,e chemometric modeling 9as per7ormed on
??4 car8oxamides as anti3/.) agents 8y di77erent ,alidated comparati,e chemometric tools.
Statistically signi7icant %<#, P<S, @F" and @F"3P<S models 9ere de,eloped. %<# model is the 8est
model 5#
2
)
S 0.OPC and #
2
Pred
S 0.CMO6. ;he 8est /1S"# model produced #
2
)
o7 0.M&4 and #
2
Pred
o7
0.O0?. Both P/"SE pharmacophore 7eatures and *isco,ery Studio 5*S6 pharmacophore 7eatures 9ere
more or less similar 9hereas the P/"SE model 5#
2
Pred
S 0.CP06 is 8etter. STBT< distill rigid, *S
pharmacophore 8ased and P/"SE 8ased alignment 9ere considered 7or o%F" and o%S." study and
*S '* 1S"# study. .t is o8ser,ed that distill rigid alignment produced 8est result 5:
2
and #
2
Pred
0.M?'
and 0.OMC respecti,ely 7or o%F" and :
2
and #
2
Pred
0.M&O and 0.&?P respecti,ely 7or o%S."6 9hereas
the *S result 9as accepta8le and P/"SE result 9as unaccepta8le. #egarding *S '* 1S"# models, all
models 9ere accepta8le 8ut *S pharmacophore 8ased model 9as the 8est 5:
2
and #
2
Pred
0.P4O and
0.CC' respecti,ely6. Electronic interaction at atom num8er M and C and '*3%o#SE and autocorrelation
descriptors play important roles 7or higher acti,ity. @reen steric, magenta hydropho8ic and
electrostatic 8lue 7a,ora8le contours near to atom num8er M and C are important 7or higher acti,ity.
;hese results may 8e use7ul to generate 8etter #P antagonists o7 this class.









1/91;+/I<I/; =u4, *E2E/*E/9 >-+,-M 'E/'I/; 1/* -/*E,'91/*I/; I9' '9,-59-,1=
5!1/;E':1 5+M2-919I+/1= 122,+15!


V.Hasthi Annapurna, V.Ashwinkumar, Prahitha T A, S. Niveda, Mr. S.Karthi

School o7 hemical and Biotechnology, S"S;#" 0ni,ersity,;hanLa,ur,;amil $adu,.ndia

1uorum3sensing 51S6 8acteria communicate ,ia small molecules called auto3inducers to coordinate
gene expression. "s 1S controls ,irulence 7actor expression in many clinically rele,ant pathogens,
mem8rane3permea8le 1S antagonists that pre,ent population39ide expression o7 ,irulence genes o77er
a potential route to no,el anti8acterial therapeutics. &. aeru,inosa 9ith B. cepacia is in,ol,ed in a 7atal
pulmonary in7ection o7 cystic 7i8rosis 5F6 patients . " set o7 'M compounds, 9hich 9ere pro,en to 8e
acti,e against <ux# proteins o7 &. aeru,inosa 5#hi#6 and B. cepacia 5ep#6 9ere chosen. "
pharmacophore model 9as generated to understand the structural 7actors a77ecting the inhi8itory
potency o7 these compounds. ;he model 9as then employed as '* :uery search to screen a data8ase
o7 compounds in order to select ne9 common inhi8itors. ;he chosen set o7 compounds 9ere then
docked to 8oth #hi# and ep#. " common inhi8itor 5?O42C2C6 9hich sho9ed 8inding a77inity to 8oth
the proteins 9as chosen 8ased on the di77erent structural criteria. ;his compound 5?O42C2C6 9as then
checked 7or its acti,ity 9ith the Penicillin Binding Protein 5PBP6, a protein 9hich plays a maLor role in
8acterial cell 9all synthesis, 7or con7irming the a8ility o7 this compound to inhi8it 8io7ilm 7ormation.
%olecular dynamics simulations o7 #hi# 9ith its auto3inducer 5".6 and the common inhi8itor 9ere
carried out 7or ?0ns each and it 9as o8ser,ed that the *$" 8inding helices mo,ed almost ?0U a9ay
7rom each other. ;his mo,ement 9ill pre,ent the 8inding o7 the transcriptional acti,ator protein to the
*$" thus stalling the transcription process. ;his ga,e an insight into the structural changes in the
protein 9hen 8ound to an inhi8itor.











Design, Synthesis, Pharmacological Evaluation and QSAR studies of benzimidazole compounds as
Antidepressant agents.

M. R. Suryawanshi, V. M. Kulkarni, S. H. Bhosale, K. R. Mahadik

In our recent publication, we have described pharmacophore generation and atom-based 3D-QSAR
analysis of previously reported MAO-A inhibitor indole derivatives, to determine the structural requirement
for high affinity towards the enzyme. The active site mapping of X-ray structure of human MAO-A
(hMAO-A, PDB: 2Z5X) was performed using Sitemap. PHASE from the Schrdinger suite 2009, was used
for generation of pharmacophore model for active compounds of the dataset. Best scoring pharmacophore
model was DHHR.67. Based on pharmacophore model, a statistically valid atom-based 3D-QSAR analysis
was performed, which included 67 molecules in training set and 15 molecules in the test set. Active
compounds were docked with crystal structure of the enzyme using Glide XP docking.

For scaffold-hopping, in silico screening of 1,40,000 compounds from ZINC clean drug like database was
performed with pharmacophore model as a query. 3D-QSAR model was used to predict activity of the hits.
Refinement of retrieved hits was accomplished by applying filters of fitness score, predicted activity and
docking score. Finally, 11 hits recovered by scaffold-hopping offer structurally varied molecules as potential
MAO-A inhibitors. Out of the 11 hits, we have selected one hit with some structural modifications. The
designed structure was then docked against the target hMAO-A for ascertaining its binding affinity. The
present series of compounds VS1 VS25 with various substitution in phenyl ring may provide better
MOA-A inhibitors. Structure confirmation of synthesized compounds was accomplished on the basis of IR,
1
H NMR,
13
C NMR, DEPT-135, MS and elemental analysis. Tail suspension test and forced swimming test
were employed for evaluation of antidepressant activity. QSAR model was developed on the basis of tail
suspension test results which correlated parameters QPPCaco, FOSA and QPpolz with biological activity.









Study of subtype selectivity of human KCNQ2/Q3 activators using ligand
based methods.

Pakhuri %ehta- and Sachin S. $arkhede
*epartment o7 Pharmacy, School o7 hemical Sciences and Pharmacy, entral 0ni,ersity o7 #aLasthan,
Bandar Sindri, *ist.3 "Lmer3'0PO0?, #aLasthan, .ndia.
E3mail: sachin.narkhede@curaL.ac.in

;he de,elopment o7 human ($12D1' channel acti,ators ha,e 8een recently reported 7or ,arious
therapeutic applications, including treatment o7 hyperexcita8ility related disorders like epilepsy and
migraine. /o9e,er, many o7 these acti,ators cause undesired side eVects through the cross3reacti,ity 9ith
other ($1 receptor su8types, mainly ($1?.
;o study the selecti,ity o7 ($12D1' channel acti,ators, it has 8een proposed to de,elop pharmacophore
models 7or 8oth acti,ators. ;he 7our point pharmacophore model 9ith acceptor, donor, hydropho8ic and
aromatic ring 7eatures 7or ($12D1' acti,ators 9as deri,ed using P/"SE. ;his pharmacophore model 9as
selected 7rom a pool, 8y correlating the o8ser,ed and estimated acti,ity 7or the training and test set o7
molecules using partial least s:uare analysis 5,alidation6. ;9el,e acti,e molecules 9ere used to de,elop
the pharmacophore model 7rom di,erse classes such as $3pyridyl and pyrimidine 8en2amides and
8en2othia2ol323ylidine hydra2ides 5reported earlier6 and C? molecules 5reported earlier6 9ere used 7or
,alidation o7 pharmacophore.
;he de,eloped pharmacophore model 7or ($12D1' acti,ators 9ould 8e used along 9ith ($1? reported
ligands 7or the study o7 the selecti,ity.








Study of subtype selectivity of human H3 histamine receptor over H4
histamine receptor using ligand based methods.

2anka7 Kumar '(arma$ and 'ac(in '3 /ark(ede
*epartment o7 Pharmacy, School o7 hemical Sciences and Pharmacy, entral 0ni,ersity o7 #aLasthan,
Bandar Sindri, *ist.3 "Lmer3'0PO0?, #aLasthan, .ndia.
E3mail: sachin.narkhede@curaL.ac.in

;he de,elopment o7 human /' histamine receptor 5h/'/#6 antagonists ha,e 8een recently reported 7or
,arious therapeutic applications, including treatment o7 "l2heimer=s disease, attention deWcit hyperacti,ity
disorder 5"*/*6, epilepsy, and o8esity. /o9e,er, many o7 these antagonists cause undesired side eVects
through the cross3reacti,ity 9ith other histamine receptor su8types, mainly human /4 histamine receptor
5h/4/#6.

;o study the selecti,ity o7 h/'/# antagonists o,er the h/4/# antagonist, it has 8een proposed to de,elop
Pharmacophore models 7or 8oth antagonists. ;he 7our point pharmacophore model 9ith one hydropho8ic
7eature, one positi,e, one hydrogen 8ond acceptor and one hydrogen 8ond donor 7eature 7or h/4/# an
antagonist 9as deri,ed using P/"SE. ;his pharmacophore model 9as selected 7rom a pool, 8y correlating
the o8ser,ed and estimated acti,ity 7or the training and test set o7 molecules using partial least s:uare
analysis 5,alidation6. ;9enty t9o acti,e molecules 9ere used to de,elop the pharmacophore model 7rom
di,erse classes: 8ispyrimidines, :uina2olines, indolecar8oxamides, :uinoxalines, tria2ole5reported earlier6
and 202 molecules5reported earlier6 9ere used 7or ,alidation o7 pharmacophore.
Similarly, the re7inement o7 pharmacophore model 7or h/'/# antagonists 5reported earlier6 9ould 8e
per7ormed and used 7or study o7 the selecti,ity o,er h/4/# antagonists.











Pharmacophore Mapping Studies To Identify Novel HCV RNA Polymerase Inhibitors

Nabeela Sayed, Elvis A. F. Martis, Evans C. Coutinho and Raghuvir R. S. Pissurlenkar
#

Department of Pharmaceutical Chemistry, Bombay College of Pharmacy,
Kalina, Santacruz [E], INDIA, 400098, Correspondence: raghuvir@bcpindia.org

HCV is a positive single-stranded-RNA [(+)ssRNA] virus and a member of the Flaviviridae family.
NS5B is an RNA-dependent RNA polymerase that catalyzes the polymerization of ribonucleoside
triphosphates (rNTP) during viral RNA replication. The HCV polymerase NS5B is a very attractive target,
since better selectivity and less toxicity are possible with inhibitors targeting the viral polymerase compared
to inhibitors that target cellular pathways. RNA dependent RNA polymerases form a right-hand-like
structure with thumb, finger, and palm subdomains. In this study we report the pharmacophore mapping
studies on HCV NS5B RNA polymerase inhibitors and give insights about the ligand-interactions that can
assist drug design strategies using virtual screening.

Bibliography:
1. Kumar DV, Rai R, Brameld KA, et al. Quinolones as HCV NS5B polymerase inhibitors. Bioorg
Med Chem Lett 21 (2011);8287.
2. Ago H, Adachi T, Yoshida A, et al. Crystal structure of the RNA-dependent RNA polymerase
of hepatitis C virus. Struct l7 (1999);14171426.
3. Harper S, Avolio S, Pacini B, et al. Potent Inhibitors of Subgenomic Hepatitis C Virus RNA
Replication through Optimization of Indole-N-Acetamide Allosteric Inhibitors of the Viral
NS5B Polymerase. J Med Chem. 48 (2005);4547-4557.











QSAR STUDIES OF CERTAIN NOVEL HETEROCYCLES DERIVED FROM BIS- 1, 2, 4
TRIAZOLES AS ANTI- TUMOR AGENTS.
Stephen Philip, Madhusudan Purohit, Bharat Kumar I
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysore.

The authors reported the synthesis of 46 Bis- triazoles having various modificational groups such as diethyl
carbamoyl, thioester, hydrazide, oxadiazole and pyrazole in their previous papers. The anti- tumor
evaluation was carried out on Lung carcinoma A-549, Colon carcinoma HT-29, and Breast Cancer MDA-
MB-231. Here we report the quantitative structure activity relationship of these compounds for predicting
the activity profile of novel bis- triazoles. The full model encompassed a dataset of 46 Bis- triazoles. Tripos
Sybyl X 2.0 program was used to conduct CoMSIA QSAR modeling. The Partial Least-Squares (PLS)
analysis method was used to conduct statistical analysis and to derive a QSAR model based on the field
values of CoMSIA descriptor. The compounds were divided into test and training set. The compounds were
evaluated by various CoMSIA parameters to predict the best QSAR model. An optimum numbers of
components were first determined separately by cross-validation regression for CoMSIA model, which were
then applied in the final analysis. A series of parameters were used for the study and the best fit model was
obtained using donor, partition coefficient and steric parameters. The CoMSIA models demonstrated good
statistical results with regression coefficient (r
2
) and the cross-validated coefficient (q
2
) of 0.575 and 0.830
respectively. The standard error for the predicted model was 0.16322. In the CoMSIA model, the steric
descriptors make a marginally larger contribution than the electrostatic descriptors. The result that the steric
descriptor is the largest contributor for the CoMSIA QSAR models is consistent with the observation that
more than half of the binding site area is occupied by steric regions.
Keywords: 3D QSAR, CoMSIA, Triazoles.

QSAR and docking studies on Capsazepine analogs for immunomodulatory and anti-
inflammatory activity

Aparna Shukla
1
, Pooja Sharma
1
, Suaib Luqman
2
, D.U. Bawankule
2
, S.K. Srivastava
3
Feroz Khan
1
*
1
Metabolic and Structural Biology Department,
2
Molecular Bioprospection Department,
3
Medicinal Chemistry Department, CSIR-
Central Institute of Medicinal & Aromatic Plants, Lucknow- 226015, India, E-mail: f.khan@cimap.res.in


A quantitative structure activity relationship (QSAR) regression model was developed for immunomodulatory and
anti-inflammatory activity of Capsazepine analogs/derivatives targeting proinflammatory mediators IL-1 and TNF-.
QSAR model was derived through multiple linear regression method using leave-one-out validation approach.
Activity prediction accuracy of derived QSAR model was indicated by statistical measures viz., regression coefficient
(r
2
= 0.88) and cross validation regression coefficient (r
2
CV = 0.81). The QSAR study indicates that chemical
descriptors viz., electron affinity, HOMO energy and Lambda Max UV-visible (nm) are correlated well with the
activity. Furthermore, seven Capsazepine analogs viz., CPZ-1, CPZ-2, CPZ-3, CPZ-4, CPZ-5, CPZ-6 and CPZ-7 out
of twenty four query set compounds were screened for activity. Predicted active Capsazepine analogs were subjected
to molecular docking studies for detecting target specific binding affinity and lastly screened through standard
electronic parameters of drug likeness, ADME and toxicity risk. In experimental validation step, predicted results of
Capsazepine was confirmed through in vitro studies on Swiss albino mice proinflammatory mediators IL-1 and TNF-
. Besides, a total of 44 Capsazepine designed derivatives were also evaluated through derived QSAR model for
putative activity. Chemical semi-synthesis, structure elucidation by NMR and experimental in vitro studies for
immunomodulatory and anti-inflammatory activity of predicted active derivatives of Capsazepine are in progress. The
obtained results in the present work will be fruitful for the design of potent inhibitors of proinflammatory mediators.
Keywords: QSAR, Docking, ADMET, Capsazepine, Immunomodulatory, Anti-inflammatory.










INSILICO STUDIES ON IDENTIFICATION OF ACTIVE COMPOUNDS
FOR GLYCOGEN SYNTHASE KINASE 3-BETA PROTEIN.


E.PREETHI, KB.SANJANA, J.B. SHEEMA,

WAHEETA HOPPER


Department of Bioinformatics, SRM University. Email: sakti.preethi@gmail.com


The wound healing activities of plants have since been explored in folklore. Several plants and herbs
have been used experimentally to treat skin disorders, including wound injuries in traditional Indian
medicine. It has been proven that Wnt/b-catenin pathway can enhance wound healing through the
inhibition of GSK3-beta protein which is an important regulatory enzyme. Number of phytoconstituents
from Indian medicinal plants were collected from literature. The objective is to find one or more compounds
based on the similar pharmacophoric group which interacts with that target, and in doing so blocks the given
target. The active site of the GSK-3 beta protein was predicted using SiteMap tool in Schrdinger software.
The developed pharmacophore model was screened with a database of more than thousand compounds to
find out novel compounds with similar pharmacophore features that can act as potentially active compound
against GSK-3. Docking simulation of GSK-3 Beta Protein and the novel compounds was performed using
the Glide docking program in Schrdinger software. Compounds identified by screening were ranked
according to the information obtained by different scoring constraints. The highest scoring compounds were
selected for further evaluation. After visual inspection, the most favorable compounds with the best binding
modes (high glide score and length of the hydrogen bond) were selected. The inhibitor(s) will be further
validated using animal models.
Keywords: GSK-3, Wnt/b-catenin pathway, Wound healing, Pharmacophore model, Docking simulation.










PHAMACOPHORE BASED STUDIES ON
IDENTIFICATION OF ACTIVE INHIBITORS FOR
ALZHEIMERS DISEASE


RAGHAVI SURESH8 J.B. SHEEMA, Dr. WAHEETA HOPPER
Department of Bioinformatics, SRM University. Kattankulathur
,Tamilnadu 603203, India, Email: raghavisrsh93@gmail.com


Alzheimers Disease (AD) is an escalating national epidemic. Alzheimers the most
common form of dementia, is a progressive brain disease. Research indicates that the
disease is associated with plaques and tangles in the brain. Alzheimer's disease (AD) is a
devastating neurodegenerative disorder with a relentless progression. AD pathogenesis is
believed to be triggered by the accumulation of the amyloid-B peptide which is due to
overproduction of Amyloid beta and the failure of clearance mechanisms. The objective
is to find best compound(s) based on the similar pharmacophoric group which interacts
with the target, and blocks the given target. The active site of the Amyloid beta protein
was predicted using Schrdinger software. The developed pharmacophore model was
screened with a database to find out novel compounds with similar pharmacophore
features that can act as potentially active compound against Amyloid beta . Docking
simulation was performed using the Glide docking program. The highest scoring
compounds were selected for further evaluation. Efforts are being devoted to acquire a
clear understanding of how all these molecules and structures work in normal neurons,
and what goes haywire in the subjects that go on to develop AD and also analyze
advantages and potential drawbacks through laboratory diagnosis of Alzheimers
Disease.
KEYWORDS: Alzheimers Disease, Amyloid Beta peptide, Pharmacophore, Schrdinger
software, Glide docking .








Design and Synthesis of p38 Kinase inhibitors- A Computational approach

Ravindra Kulkarni
1*
, Achaiah G
2*
, Prashant Gurav
1
, Patsil JS
1
, Amarnath B
1
,


1. SVERIs College of Pharmacy, Gopalpur, Pandharpur -413 304
2. UCPSC, Kakatiya University, Warangal, Andhra Pradesh


P38 kinase is well known for its role in the production and release of elevated levels of pro-
inflammatory cytokines in numerous inflammatory diseases. Due to this, p38 kinase now has been attracted
the attention of medicinal chemists as an important validated target for drug discovery. The development of
first generation and allosteric p38 kinase inhibitors has opened new prospect for the development of potent
and safe agents for inflammatory diseases. In this communication, we report the design of new allosteric
binding diaryl urea compounds and ATP site binding benzimidazoles as p38 kinase inhibitors.
Series of pyrazolyl urea p38 kinase inhibitors have been selected to understand the properties that
influence activity by using CoMFA and CoMSIA. These QSAR tools resulted in best models with favorable
statistical data and based on such models few new molecules were designed and docked in allosteric binding
pocket of p38 kinase. We noticed that if an additional hydrogen bond interaction between an acceptor of
kinase inhibitor with M109 apart from regular hydrogen bond interactions enhanced the p38 kinase
inhibitory activity.
From the newly designed molecules, we attempted to replace pyrazole moiety by substituted phenyl
group and observe influence on p38 kinase activity. One such compound bearing 4-iodophenyl group
demonstrated in vitro p38 kinase inhibitory activity with IC
50
value of 1.09 M and 79.41% inhibition of rat
paw edema. Further, the docking studies of newly synthesized compounds revealed a missing hydrogen
bond interaction in DFG out pocket.
The urea compounds were further modified into benzimidazoles and synthesized them. Several of the
2-unsubstitueted phenyl benzimidazoles demonstrated greater than or equal to 50% inhibition of p38 kinase
at 10 M concentrations. Docking studies of such molecules disclosed different binding interactions.








Pharmacophore-based 3D-QSAR studies of CCR3 Inhibitors: A chemical optimization
of a potent antagonist for the treatment of allergic disease
Shuba Dixit
1
, Richa Verma
1
, Thirumurthy Madhavan
1
*
1
Department of Bioinformatics, SRM University, SRM Nagar, Kattankulathur-603203, Tamilnadu, India
*
Email: thiru.murthyunom@gmail.com, thirumurthy.m@ktr.srmuniv.ac.in

Chemokine receptors belong to the member of G-protein coupled receptors (GPCRs), which plays important
role in the treatment of asthma. The quantitative structure activity relationship (QSAR) study was performed
to explore the significant chemical features of CCR3 antagonist. A set of 30 antagonists were utilized to
construct 3D-QSAR model containing 23 in the training set and 7 in the test set. Since there is a lack of X-
ray crystal structure information for CCR3, the pharmacophore-based QSAR techniques would be realistic
approach. Common feature pharmacophore models were developed from the known antagonist using Phase
module in Maestro. The best pharmacophore model containing one hydrogen bond acceptor, one hydrogen
bond donor, two hydrophobic and one positively charged features were selected and validated. Various
QSAR models were generated, the optimum model was chosen based on the statistical values of q
2
=0.9228,
and r
2
=0.9315. Statistical parameters from the generated QSAR models indicated that the data is well fitted
and have high predictive ability. The Phase QSAR models predicted important positive and negative
parameters that are important for activity toward CCR3. Our theoretical results could be useful to design
novel and more potent CCR3 derivatives.

Keywords: GPCR. CCR3. Pharmacophore hypothesis, 3D-QSAR





QSAR model for predicting inhibitory activity of COX-2 inhibitors
Sandhya. V, Jhinuk Chatterjee, Biplab Bhattacharjee
Department of Biotechnology, PES Institute of Technology, Bangalore-560085.

Quantitative structure activity relationship (QSAR) plays a key role in drug discovery
and development. It involves steps such as: Data set preparation, Descriptor
calculation, Attribute selection, Model building, and Performance evaluation.
CycloOxygenase-2 (COX-2) inhibitors are known to serve as chemopreventive agents in a
wide spectrum of human cancers. In this study, QSAR models have been constructed for
prediction of pIC
50
values of COX-2 inhibitors using machine learning algorithms
.

Predictive regression models were built based on molecular descriptors by employing
methods such as Sequential Minimal Optimization (SMOreg) and Multiple Linear Regression
(MLR) in WEKA 3.6.8 software. This was followed by internal cross-validation using
Leave One Out Cross-Validation (LOOCV) procedure and external cross-validation on an
independent data set. Our observations reveal that SMOreg based model performs better
than MLR based model in terms of Squared Correlation Coefficient, Mean Absolute Error,
Root Mean Squared Error and Cross-validated squared correlation coefficient
respectively. Highest correlation was achieved for largest training set and smallest
test set using SMOreg method on external data set. This predictive model will aid drug
discovery community in knowing the bioactivity of their compound library, prior to
experimental studies, thereby saving the cost and time involved in research studies.


Design of novel peptidomimetic glucokinase activators for Type-2 Diabetes using
energy based pharmacophore approach


Saradindu Ghosh
1*
, Puniti Mathur
2

1. Amity Institute of Biotechnology, Amity University (UP), ghosh.saradindu@gmail.com
2. Amity Institute of Biotechnology, Amity University (UP), pmathur@amity.edu


Owing to the unique function in regulating glucose metabolism, glucokinase has drawn special attention as a
drug target for type-2 diabetes. Glucokinase (GK), an enzyme that phosphorylates glucose to glucose 6-
phosphate, serves as the glucose sensor that regulates insulin secretion in pancreatic beta cells. GK
activators (GKAs) activate GK via binding to an allosteric site of the enzyme. GKAs increase glucose
stimulated insulin secretion and regulate blood glucose levels. In the present study, a novel class of peptide-
based GKAs was designed based on the compounds RO281675, piragilatin, PSN-010, LY-2121260, ARRY-
588, well-known carbon centered GKAs, using Glide docking and E-pharmacophore techniques. Glide
docking depicted that the designed peptide-based GKAs have better relative binding affinity than
RO281675, piragilatin, PSN-010, LY-2121260, ARRY-588. It also showed additional pi-pi interactions of
some of the designed ligands with the receptor. It was further validated by the outcome of their E-
pharmacophore rank and pharmacophoric features that the designed peptide based GKAs can be potential
glucokinase activators.












QSAR modelling, Docking and ADMET studies on Xanthone derivatives/analogs for Anti-
proliferative activity in human HeLa cancer cell line

Sarfaraz Alam
1
, Feroz Khan
1
*, Om Prakash
1
, Dnyaneshwar U. Bawankule
2
, Santosh K. Srivastava
3
, Suaib
Luqman
2

1
Metabolic and Structural Biology Department,
2
Molecular Bioprospection Department,
3
Medicinal Chemistry
Department, CSIR-Central Institute of Medicinal & Aromatic Plants, Lucknow- 226015, India, E-mail:
f.khan@cimap.res.in


Due to the high mortality rate of cancer patients, identification of novel as well as potent molecules is
important for the development of anticancer drugs. Xanthones are the natural constituents of Bonnetiaceae
and Clusiaceae family plants. They have oxygenated heterocyclic moities responsible for a variety of
biological activities along with anticancer effect. To screen the anticancer compounds from xanthone
derivatives, a quantitative structure activity relationship (QSAR) model was developed by using multiple
linear regression method. The structureactivity relationship represented by the QSAR model yielded a high
activitydescriptors relationship accuracy of 84% refer by regression coefficient (r
2
= 0.84) and a high
activity prediction accuracy of 82% refer by cross validation regression coefficient (rCV
2
= 0.82). Five
molecular descriptors viz., dielectric energy, hydroxyl group count, LogP, shape index basic (order 3) and
the solvent accessible surface area were found significantly correlated with the anticancer activity. A set of
virtually designed xanthone derivatives were screened for anticancer activity by newly derived QSAR
model. Molecular interaction study through docking method was performed with a LibDock protocol of
Discovery Studio v3.5 (Accelrys Inc., USA, 2013). Docking studies was done to explore the mechanism of
action of predicted lead compounds on human anticancer targets DNA Topoisomerase II. The
pharmacokinetics parameters like ADME and toxicity risk were also calculated. SYLVIVA scores were
calculated to validate the synthetic accessibility of predicted leads. The strategy used in this study may
provide helpful understandings in designing novel DNA Topoisomerase II inhibitors.
Keywords: DNA Topoisomerase, Drug likeness, ADMET, QSAR, Docking, HeLa cancer cell line









Screening of skin sensitization potential of diverse organic chemicals through the
development of classification- and regression-based QSAR models



Ashis Nandy, Supratik Kar and Kunal Roy*
Drug Theoretics and Cheminformatics Laboratory,
Department of Pharmaceutical Technology,
Jadavpur University, Kolkata 700032, India


With the rapid advancement of the worlds population and combined with the industrial progress, there is a
significant impact of chemicals including pharmaceuticals on the worlds ecosystems. A chemical may
induce B-cell and T-cell infiltration from lymph nodes resulting in irritation of skin and carcinoma on
prolonged use. To minimize the animal study and also to reduce time and expenditure, development of in
silico predictive models has achieved a considerable attention over the last few decades. In this study, we
have developed classification- and regression-based QSAR models for skin sensitization potential of 67
diverse organic chemicals. The developed models strongly suggest the importance of the number of H atoms
in a molecule inferring that the unsaturated compounds are more skin-sensitizing agent than the saturated
compounds. Other two descriptors, c
v

3
and nCb-, signify the importance of the lipophilic character of the
molecules. Here, we have also screened the DrugBank database (http://www.drugbank.ca) containing a large
number of compounds using our developed models in an attempt to identify molecules with skin
sensitization potential.

















Synthesis, antitubercular evaluation and field based 3D QSAR study of pyrazole derivatives

S. G. Alegaon*, K. R. Alagawadi, D.H. Dadwe
Department of Pharmaceutical Chemistry, KLE Universitys College of Pharmacy, Nehrunagar, Belgaum-
590 010, Karnataka, India, E-mail address: sgalegaon@klepharm.edu


Novel pyrazole derivatives were efficiently synthesized and evaluated for their in vitro antitubercular
activity against Mycobacterium tuberculosis (MTB). The chemical structures of the compound were
elucidated by elemental analysis, IR,
1
H NMR, and mass spectral data. Most of the title compounds have
exhibited significant antitubercular activity. Compounds 4g, 4h, 4l, 4n and 4o showed pronounced
antitubercular activity comparable to the isoniazid (INH). One of these compound 4g showed high activity
against MTB (MIC = 0.39 g/ml). We performed in silico field based 3D QSAR and molecular docking
using crystal structure data for the mycobacterium tuberculosis enoyl reductase (PDB id; 2H7M). We found
that hydrophobic backbone and side chain interactions are with Ser94, Gly96, Met147, Ash148, Gly192, and
Ile194. The polar residues Lys 165 and Tyr 196 have uniform influence with synthesized compounds and H
bonding of all the compounds with Tyr 158, and field based 3D QSAR had suggested the optimization
options in our scaffold and contribution of steric, electrostatic, Hydrophobic, H bond acceptor and H bond
donor in the core Imidazo [2, 1-b]thiazole.















Pharmacophore Modelling and Docking Simulations Based Hierarchial Virtual Screening Protocol:
Designing of Multi-Targeted Agents for Interleukin -2-inducible T-cell Kinase (ITK) and Interleukin-
1-Receptor Associated Kinase (IRAK-4) Inhibitors.

Siddharth Upadhyay and Om Silakari*
Molecular Modeling Lab (MML), Department of pharmaceutical Sciences and Drug Research, Punjabi
University, Patiala, 147002, *E-mail: omsilakari@rediffmail.com

Immune system, a complex of biological structures within an organism, provides protection from various
disease causing pathogens by identifying and killing them. The immune system is categorized into innate
and adaptive immune systems. Innate immune system acts as a first line of defense, protects the host from in
a non specific manner, and provides a temporary, not long lasting protection through natural killer (NK)
cells, macrophages and dendrite cells. On the other hand, adaptive immune system provides a second line of
defense, and is comprised of highly specialized cells including T and B lymphocytes. Although the induced
immune response favours the host by neutralizing or destroying the harmful pathogens, sometimes it
commits a mistake and consider its normal body tissues as enemy and build up antibodies to destroy them
resulting in autoimmune disorders, such as rheumatoid arthritis, Crohns disease, psoriasis, and myasthenia
gravis etc. Therefore, the small molecules that can modulate the abnormal activation of immune systems
may serve as potential therapeutic agents for the treatment of above mentioned disorders.
ITK and IRAK-4, the members of Tec family of non-receptor protein tyrosine kinases and
serine/threonine specific kinases, respectively, are such kinases which reduce the over-expressed
inflammatory/immune responses. IRAK-4 mediates the innate responses acting through toll like receptors
(TLRS) while ITK mediate adaptive responses through activation, proliferation, and differentiation of T-
cells. Therefore, the molecules having dual inhibitory potential against ITK and IRAK-4 would serve as
novel and better anti-inflammatory agents for the management of inflammatory disorders.
With the aim to design dual inhibitors of ITK and IRAK-4, the reported molecules against both
targets were considered to develop pharmacophore models. The generated pharmacophore models against
both targets were validated on the basis of several validation parameters, such as Y-randomization test,
applicability domain calculation, test set prediction, GH score, and enrichment factor calculations etc. The
validated models for both targets were then utilized for the screening of PHASE molecular database, which
retrieved different new chemical scaffolds. Out of the retrieved chemical scaffolds, 'acridone' lead was
selected for further optimization, on the basis of synthetic feasibility and reliability. Thereafter, the acridone
derivatives were synthesized and their activity profiling is under process.







Pharmacophore Modeling and 3D-QSAR Studies on Janus Kinase-2 Inhibitors

B. Siva Jyothi
1
*, V V S Rajendra Prasad
2
, P.Manichandrika
1


1
Department of Pharmaceutical Chemistry, Bojjam Narasimhulu Pharmacy college for women, Hyderabad,
AP, India. katreddyjyothi80@gmail.com
2
Medicinal Chemistry Research Division, Vishnu Institute of Pharmaceutical Education and Research,
Narsapur, India.

Janus Kinase 2 (JAK2) is an intracellular, non-receptor tyrosine kinase belonging to the family of
Janus Kinase that also includes JAK1, JAK3 and Tyk2. JAK2 is expressed ubiquitously and plays an
important role in mammalian development, physiology and. However, the recent discovery of JAK2s
acquired point mutation V617F led to greater understanding its oncogenic role in Myeloproliferative
Neoplasms (MPNs). MPNs are a group of genetic disorders that are characterized by abnormal production of
blood cells in the bone marrow. These chronic disorders are associated with specific mutations or
rearrangements resulting in the constitutive activation of growth factor receptors or cytoplasmic tyrosine
kinases. The JAK2-V617F point mutation is present approximately in 95% of patients suffering with PV and
60% of patients with either essential thrombocythemia (ET) or primary myelofibrosis (PMF). JAK2-V617F
mutation results in the substitution of valine by phenylalanine at 617 amino acid position and the
consequences of which are cytokine independence and hypersensitivity through the constitutive activation of
JAK-STAT signaling pathway.
Therefore, targeting mutant JAK2 to prevent its constitutive activation will be a promising
therapeutic option in the treatment of myeloproliferative neoplasms. In the present study we performed
pharmacophore modeling and built a 3D QSAR model for pyrido-indole derivatives of Janus Kinase 2
inhibitors. An efficient pharmacophore has been identified from a data set of 51 molecules and the identified
pharmacophore hypothesis consists of one hydrogen bond acceptor, two hydrogen bond donors, and three
aromatic rings i.e., ADDRRR. A powerful 3D-QSAR model was constructed by employing Partial Least
Square regression analysis with a regression coefficient of 0.97 (R2) and Q2 of 0.95, and Pearson-R of 0.98.







Surfing molecular axioms against malaria to find novel pfDHODH inhibitors utilizing
shape similarity fragment guided virtual screening and chemogenomic analysis.


Subhadip Banerjee
1
, Anil K Saikia
2

1 Bengal Institute of Pharmaceutical Scinces. Jadavpur University.Kolkata.West Bengal.
2 Department of Pharmaceutical Sciences. Dibrugarh University. Dibrugarh. Assam



Malaria is continuing its existence as a major killer all over the world. Recent reporting of artimisinin
resistant malaria make discovery of novel anti-malarial leads a principle necessity. Surfing through the
diversity in search of bioactive chemical structures on the basis of shape similarity has been a priceless tool
in computer-aided drug design, principally in the milieu of virtual screening. Its successful relevance has
been published in various literatures, such as scaVold hopping, bioisostere replacement, virtual library
design, and exible ligand superposition. Another new method in the drug discovery arena is fragment-
based drug design and fragments (number of heavy atoms 22) have been used as the initial stepping stone
of hit optimization. Target guided drug discovery combined with fragment based methods can be a effective
tool for virtual screening because of its efficiency to explore chemical space and new protein ligand
interactions have been well acclaimed in various high throughput studies with active hit retrieval. In our
present work, we have reported a novel application paradigm utilizing fragment based e-pharmacophore
generated using energy stable docked poses of fragments against DHODH receptor using Glide at extra
precision mode to search for diverse compounds from the Chembl-NTD + Gsk malaria whole cell screening
database. The top scoring hits were docked into the target to find their original binding affinity. Then we
selected those ligands with favourable Glide gscores (less than-7.00) to build a focused set of diverse
hits.This compounds from Tres Cantos Anti-malarial TCAMS dataset contains for over 13,500 compounds
confirmed to inhibit parasite growth by more than 80% at 2 uM concentration. The diverse chemical library
has been hypothesized to contain pfDHODH inhibitors which are our prime concern. Since novel core is not
available against pfDHODH target it's a prime concern to search new bioactive cores. To achieve that goal ,
first we designed compounds with novel cores from active triazolopyrimidine using shape based core
hopping, then we screened our hypothesis to be stable to our target employing docking, the hits were then
used as query to screen our focused database prepared previously using shape based similarity calculated by
Phase Shape of Schrodinger . The top hits were then analyzed for their promiscuity using chemogenomic
approach on the basis of tanimoto similarity between the hits and the mode of action hypotheses molecules.
The results showed commendable coverage of chemical space and discovered existence of novel leads as
starting points towards development of pfDHODH inhibitors with novel cores.






MMP-8 inhibition: Combined structure and ligand based pharmacophore model to
identify the potent inhibitors against rheumatoid arthritis


Sukesh Kalva
1
, Lilly M Saleena
1*

1
Department of Bioinformatics, SRM University, SRM Nagar, Kattankulathur - 603 203, Kancheepuram District,
Chennai, India.


MMP-8 is the key mediator to initiate type I collagen degradation and is associated with rheumatoid arthritis. In the
present study, a hypotheses was developed based on selective non zinc binding inhibitors of MMP-8. The
pharmacophore hypotheses were manually refined and validated by observing structures and the interactions of MMP-
8 inhibitors. The refined pharmacophore model was able to discriminate the non-zinc binding inhibitors of MMP-8
with other inhibitors. Hence this study proposes a combined structure and ligand based pharmacophore model that is
suitable for retrieving the novel inhibitors of MMP-8. The pharmacophore hypothesis AADRH was used as query for
retrieving the potential compounds from Zinc database. Using QPLD, the best 6 compounds were selected based on
selective aminoacid interactions that are catalytically important for the function of MMP-8. The 6 compounds were
further processed against different subtypes MMPs to check the selectivity profile. Finally ZINC00673680 bearing
Gscore -9.97Kcal/mol were subjected to molecular dynamics simulation to determine the stability of the predicted
conformations. From MD studies we found that ZINC 00673680 forms a stable interaction with the key amino acid
residues and avoid the zinc atom with the distance of 5.49. Moreover DFT study is also performed to confirm the
molecular electrostatic profile of the compounds. This structure based approach study will be useful for further
development of novel inhibitors with high potency and selectivity against MMP-8.








*iscovery of /ovel Molecular 'caffolds for &asopressin &
.)
1ntagonist -sing
2(armacop(ore ?ased &irtual 'creening

1nirud( &3 ?ellu)i8 Elvis 13 @3 Martis8 ,ag(uvir ,3 '3 2issurlenkar and Evans 53 5outin(o
#
*epartment of 2(armaceutical 5(emistry8 ?om)ay 5ollege of 2(armacy8 Kalina8 'antacruz AEB8 Mum)ai8 I/*I1 4CC
CDE8
#
5orrespondence: evansF)cpindia3org

;he )asopressin )
?8
receptor su8type is in,ol,ed in the regulation o7 adrenocorticotropin hormone 5";/6
release 7rom the pituitary gland, in the regulation o7 social 8eha,ior and in the regulation o7 insulin release 7rom the
pancreas
J?K.
Based on )
?8
receptor 7unction and distri8ution, selecti,e )
?8
receptor antagonists ha,e 8een suggested
as potential therapeutic agents in the treatment o7 diseases characteri2ed 8y an excessi,e cortisol secretion, such as
maLor depression and stress3related disorders
J2,'K
. Ie report the pharmacophore mapping studies on ,asopressin )
?8
antagonists and gi,e insights a8out the ligand3interactions that can assist drug design strategies using ,irtual
screening.

,eferences:
1. Lee, B.; Yang, C.; Chen, T. H.; Al-Azawi, N.; Hsu, W. H. Am. J. Physiol. Endocrinol. Metab. 1995, 269,
32.
2. Aquilera, G.; Rabdan-Diehl, C. Regul. Pept. 2000, 96, 23.
3. Scott, L. V.; Dinan, T. G. Life Sci. 1998, 62, 1985.








5o,I=I'1: a novel *->'1, met(od for compre(ending t(e t(ermodynamic events involved in drug-receptor
interactions

&i7ay M3 K(edkar and Evans 53 5outin(o

5omputer-1ided Molecular *esign =a)oratory8 *epartment of 2(armaceutical 5(emistry8 ?om)ay 5ollege of 2(armacy8
Kalina8 'antacruz (E"8 Mum)ai8 India3

" no,el :uantitati,e structure3acti,ity relationship 51S"#6 approach termed o#.<.S" 5deri,ed 7rom o#."
and <.S"6 has 8een de,eloped. ;he 7ormalism is 8ased on the calculation and comparison o7 similarity 8et9een the
molecules 5in terms o7 a local similarity index, <S.6 at each residue in the receptor acti,e site. ;he local similarity
indices at all the residues surrounding the molecules are then used as descriptors in the 1S"# 7ormalism, and the
models are deri,ed 9ith genetic algorithm incorporated partial least s:uare analysis statistics. ;he maLor highlights
o7 the 7ormalism are: 5a6 adaptation o7 the 1S"# 7ormalism in a receptor setting to ans9er 8oth the type
5:ualitati,e6 and the extent 5:uantitati,e6 o7 ligandGreceptor 8inding! 586 glo8al molecular similarity is 8roken into
local similarity at each residue surrounding the molecules gi,ing an account o7 the complete thermodynamics o7 the
ligandGreceptor 8inding. ;he methodology 9as de,eloped using the complexes o7 @lycogen phosphorylase * 9ith its
inhi8itors as a test 8ed and 9as ,alidated using t9o additional datasets3 /.)3? protease and yclin dependent kinase
2 inhi8itors. ;he 1S"# models are 7ound to 8e compara8le to the ones o8tained 8y omparati,e #esidue .nteraction
"nalysis 5o#."6, omparati,e molecular Weld analysis 5o%F"6 and omparati,e molecular similarity indices
analysis 5o%S."6 techni:ues. ;he primary o8Lecti,e is to extract not only 7rom the re7erence molecule 8ut also 7rom
the remaining ones in the series, the crucial 7eatures 9hich contri8ute positi,ely to the 8iological acti,ity and utili2e
them to design no,el compounds andDor optimi2e existing leads. ;he o#.<.S" models permit an understanding o7
the 8inding mechanisms o7 ligand 9ith the en2yme and can also 8e used to identi7y crucial interaction o7 inhi8itors
9ith the en2yme at the residue le,el. ;he generality o7 the method and the trans7era8ility o7 the protocol 9ith
essentially no changes to any other protein3ligand system are emphasi2ed.





Development of structure activity correlation model using 3D-QSAR, pharmacophore and docking studies
on thiophene derivatives as antitumor agent.

Vijay Kumar Patel*, Avineesh Singh, Deepak Kumar Jain, Harish Rajak.
S.L.T. Institute of Pharmaceutical Science, Guru Ghasidas Central University, Bilaspur (C.G.) 495009, India.
E-mail: vijay0305@gmail.com

Three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophore model and docking
studies was performed on a series of thiophene derivatives as antitumor agent and establish structure activity
correlation. 3D-QSAR models using set of 50 compounds of thiophene derivatives as tubulin-binding agents
for antitumor activity. Six-point common pharmacophore hypotheses were selected for alignment of all
compounds. The 3D-QSAR models generated using training set of 36 compounds and test set of 14
compounds showed good partial least squares statistical results. The developed common pharmacophore
hypothesis (CPHs) and 3D-QSAR models were validated further externally by predicting the activity of
database of compounds from literature and comparing it with actual activity. We have selected the 3D-
QSAR models generated by CPHs AAAHRR.32, AAHHRR.9 and AAAARR.71 for correlating the structure
with activity. Docking studies were also carried out for all compounds on colchicine-binding site of -
tubulin for studying of binding affinity of compounds for antitumor activity. The results of these molecular
modeling studies are helpful to refine the pharmacophore for design of new potential compounds for
antitumor activity.



Energy optimized pharmacophore approach to identify potential hotspots during
inhibition of Class II HDAC Isoforms.

'(a)ir 1(mad ;anai
.
8 Kart(i '(anmugam
0
8&i7ayalaks(mi Ma(adevan
.80$


?
enter 7or $anotechnology A "d,anced Biomaterials, S"S;#" 0ni,ersity, ;irumalaisamudram, ;hanLa,ur M?'40?,
;amil $adu, .ndia.
2
*epartment o7 Bioin7ormatics, School o7 hemical A Biotechnology, S"S;#" 0ni,ersity, ;irumalaisamudram,
;hanLa,ur M?'40?, ;amil $adu, .ndia Email : sganai@scbt.sastra.edu

/istone *eacetylases 5/*"s6 are conLugated en2ymes that modulate chromatin architecture 8y deacetylating
lysine residues on the histone tails leading to transcriptional repression. Pharmacological inter,ention o7
these en2ymes 9ith small molecule inhi8itors called /istone *eacetylase .nhi8itors 5/*"i6 ha,e sho9n
enhanced acetylation o7 the genome and are hence emerging as potential targets at the clinic. ;ype speci7ic
inhi8ition o7 class .. /*"s ha,e sho9n enhanced therapeutic 8ene7its against de,elopmental and
neurodegenerati,e disorders. /o9e,er, the structural identity o7 class speci7ic iso7orms limits the potential o7
their inhi8itors in precise targeting o7 their en2ymes. *i,erse strategies ha,e 8een implemented to recogni2e the
7eatures in /*" en2ymes 9hich may help in identi7ying iso7orm speci7icity 7actors. ;his 9ork attempts a
computational approach that com8ines in silico docking and energy optimi2ed pharmacophore 5epharmacophore6
mapping o7 eighteen kno9n /*" inhi8itors and has identi7ied structural ,ariations that regulate their
interactions against the six class.. /*" en2ymes considered 7or the study. .t is o8ser,ed that histidines 9ere
predominantly in,ol,ed in the hydrogen 8onding patterns 9ith /*" inhi8itors 8elonging to di,erse groups. ;he
interaction pro7iles esta8lish that the X3X interactions in lass ..a /*"s are dri,en 8y phenylalanine and
histidine residues as against histidine, tyrosine and tryptophan in lass ..8 /*"s. X3X interactions could not 8e
o8ser,ed in the linker regions o7 cyclic tetrapeptides and short chain 7atty acids. ;his com8ined approach also
esta8lishes that inhi8itors possessing higher num8er o7 aromatic rings in di77erent structural regions might 7unction
as potent inhi8itors 9hile inhi8itors 9ith scarce ring structures might point to compromised potency. ;he
o8ser,ed di77erences in pharmacophore 7eatures 9ould through ,irtual screening, aid the rationale 7or design o7
iso7orm selecti,e /*" inhi8itors 9ith enhanced a77inity and therapeutic e77iciency.

(ey9ords: /istone deacetylases . /istone deacetylase inhi8itor . %olecular docking . %olecular
%echanics @enerali2ed Born Sur7ace "rea . Energy optimi2ed pharmacophore






;1=1GH Iorkflow for E-'tate Inde4 5alculation: 1pplication in *rug *esign
Harish Jangra, Neha Tripathi, Abhaysinh M. Mori, Prasad V. Bharatam
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER),
Sector-67, S. A. S. Nagar, Mohali, 160062, Punjab, India
Email: pvbharatam@niper.ac.in
@alaxy is a scienti7ic 9ork7lo9 management system a,aila8le 8oth as an open3source so7t9are as 9ell as
9e8 ser,er 7or data intensi,e 8iomedical research. .ts graphical user inter7ace can 8e extensi,ely used to
8uild multi3step computational analyses alongside per7orm, reproduce, and share the complete analyses.
Electro3topological state 5E3state6 indices characteri2e the electronic and graph3topological en,ironment o7
each skeletal atom in a molecule. ;hese indices help in characteri2ing the 8iological interactions o7
molecules 9hich are in7luenced 8y the electronic distri8utions o7 the molecular patterns. ;his gi,es E3state
indices a potential scope in the esta8lishment o7 1S"# and 1SP# models. /ence, 9e ha,e de,eloped a
module and incorporated it into the @alaxy plat7orm 9hich calculates the E3state o7 all the molecules o7
any particular series, correlates it 9ith their .
P0
,alues to de,elop a 1S"# model. ;his module 9as
,alidated using ,arious datasets to check its relia8ility.





#e7erence:
/all, <. /.! (ier, <. B. "n electrotopological3state index 7or atoms in molecules. &harm. 2es. .DDC, C, O0?3O0C.





.nput
7ile
E3State
alculation
1S"#
model
1S"#
E:uation
Integrated Pharmacophore and Docking based Designing of New Dual Inhibitors of Colony-
stimulating Factor-1 Receptor (cFMS) and Janus Kinase 3 (JAK3).
Maninder Kaur, Pratibha Duggal and Om Silakari*
Molecular Modeling Lab(MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi
University, Patiala, Punjab, 147002, India
*Corresponding Author, Tel: +919501542696, Email:omsilakari@rediffmail.com
Protein Tyrosine Kinases (PTKs) play a crucial role in T-cell signalling and also in regulation of cellular
activation, proliferation and differentiation. Anomalous regulation of T-cell signalling pathways and above
mentioned cellular processes can lead to various autoimmune and cancerous diseases. In the present study,
the diverse inhibitor molecules of two PTKs i.e. cFMS and JAK3 were considered for pharmacophore and
docking analyses to design new multi-targeted agents for these two enzymes. Their common role in
autoimmune diseases and cancer development offers the potential to inhibit both kinases to combat disease
conditions associated with them.

The pharmacophore models were developed for cFMS and JAK3 inhibitors using PHASE module of
Schrodinger software. The generated pharmacophore models for both enzymes were clustered and top five
and six models for both targets respectively were selected on the basis of survival inactive score,
consequently used for 3D-QSAR analysis. The best model for cFMS (AAPRR.49
4
) and JAK3
(ADDRR.142
4
) were selected corresponding to highest Q
2
. AAPRR.49
4
showed R
2
=0.889 and Q
2
=0.619
whereas ADDRR.142
4
yielded R
2
=0.869 and Q
2
=0.655. Both models were employed for the systematic
virtual screening and the retrieved hits were further screened employing docking simulations with cFMS and
JAK3 proteins. Finally, the screened compounds having structural features of both pharmacophore models
and displaying essential interactions with both proteins were investigated for ADME properties. Thus, the
new leads obtained in this way would show inhibitory activity against cFMS and JAK3, and may serve as
novel therapeutic agents for the treatment of inflammatory and autoimmune disorders.


Discovery and evaluation of new leads for competitive Glycogen Synthase Kinase-3
Inhibitors through pharmacophore and docking studies
Darshit Shah
1
, C. Loganathan
2
, Ramanathan M.
1
, P. Rani
3
, S. Kabilan
2

1
Department of Pharmacology, PSG College of Pharmacy, Peelamedu, Coimbatore
2
Department of Chemistry, Annamalai University, Chidambaram
3
Department of Biotechnology, PSG College of Technology, Peelamedu, Coimbatore


Glycogen synthase kinase-3 is a multi functional enzyme, regulating various physiological functioning.
GSK-3 is up regulated in various pathological states like mood disorders, neuroinflammatin, diabetes,
cancer, Alzheimers Disease and stroke. There are no such approved drugs in market for clinical practice.
Very few drugs being used for research purpose and partially lagging specificity for this kinase. Hence aim
of this study is to identify ATP competitive novel scaffolds that can deal with GSK-3. Study belongs to the
virtual screening of database through ligand based pharmacophore and structure based docking study. Study
has initiated with generation of 3D-QSAR model using Phase, Schrodinger software with selective dataset
of 135 molecules of scaffold diversity. Valid pharmacophore extracted two acceptors, one donor and three
ring moiety (AADRRR) as a pharmacophore from active molecules. Valid pharmacophore was used to
screen SPECS database to isolate inhibitors. Screened inhibitors were filtered by standard and extra
precision modes docking using Glide, Schrodinger gave 5 hits. These hits ware screened through GSK-3
enzyme inhibition assay to find out IC50 concentration. These hits showed micromole range of activity.




A Multifaceted Approach for P-gp Substrate Prediction


Sandip Waghmare,
a
Rahul P. Gangwal,
a
Rohit Bansal,
a
Mangesh Damre,
a
Abhay T. Sangamwar
a,
*
a
Department of
Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar,
Punjab-160062, India
* Corresponding author: Tel: 0172-2214682, E-mail: abhays@niper.ac.in



P-glycoprotein is one of the members of the ATP-binding cassette super-family and is expressed in various body tissues such
as liver, kidney, intestine, testis and brain. Over-expression of P-gp actively effluxes drugs out of the cell and decreases the
efficacy of drugs and hence it is the main cause of Multiple Drug Resistance (MDR), which leads to the failure of chemotherapy
used in the treatment of several mammalian cancers. Moreover, over-expression of P-gp in Blood Brain Barrier (BBB) has led
to the resistance to the CNS acting drugs. Due to this promiscuous behavior of P-gp, many drugs have shown poor
bioavailability and less potency. Thus, early identification of a drugs or new chemical entities whether is a P-gp substrate or not
are promising for predicting the pharmacokinetics, efficacy, safety, or tissue levels of drugs or drug candidates. There are many
models which have been developed for the prediction of substrate specificity of P-gp such as 2D and 3D QSAR, SOM,
Pharmacophore, Decision Tree and Recursive Prediction Models. We have established more effective consensus scoring
for prediction of P-gp substrates using a multiple models. The applied consensus scoring yielded higher accuracies and
contained fewer variables in comparison with previous studies.

Keywords: P-glycoprotein; Molecular Docking; QSAR; KNIME Workflow,SOM




Identifying Novel Antibacterials for Drug-Resistant Strains: Adopting Ligand and Structure Based
Approaches

Tripti Kumari, Upasana Issar & Rita Kakkar*
Department of Chemistry, University of Delhi, Delhi, India


-
orresponding author. ;el: F&???2CMMM'?'! E3mail: rkakkar@chemistry.du.ac.in

With the upsurge in the number of naturally and synthetically sourced molecules, the biological screening of
compound collections on molecular/cellular assays has become an even more challenging, time-consuming
and expensive task. In the wake of these limitations, computer-aided drug design and molecular modeling
studies have come to our rescue for speeding up drug-discovery and development by enhancing the hit rate.
Peptide Deformylase (PDF) has recently emerged as an unexploited target in the search for new
antibacterials that can combat multi-drug resistant strains. That this metalloprotein is necessarily required for
bacterial survival led to the insight that its inhibition by an appropriate inhibitor would help identify optimal
leads for novel drug discovery. We have performed PHASE pharmacophore modeling (ligand-based) on a
set of non-peptidic PDF inhibitors and proposed that a three-featured pharmacophore and 3D-QSAR model
comprising an acceptor, a donor and a hydrophobic moiety (ADD.10) shows the best internal (Q
2
= 0.667)
and external dataset (R
2
= 0.556) predictivity. The contour maps gave us the picture of the spatial positions
where the presence of these groups would enhance/diminish inhibitor potency. The model was used as a
query to mine large compound collection and those molecules that showed good fitness score with respect to
the model were obtained as hits. Glide-extra precision docking (structure-based) performed on the
obtained hits showed that they have an appreciable binding affinity for the protein, which was decided on
the basis of the Glide score, E
model
and Prime MM/GBSA Gibbs energy of binding. These novel drugs are
thus proposed as optimal leads for the inhibition of Peptide Deformylase. The proposed inhibitors have also
been studied for their ADME properties, and all of them were found to have a clean profile.
Our study has revealed three novel hydroxamate-based leads that might be carried forward for in vivo
studies as PDF inhibitors. We have retrieved new leads as PDF inhibitors and thus conclude that virtual
screening is a promising method in the drug development program with wide scope and applicability.



Synthesis and Molecular modeling studies of novel acridone derivatives as P-glycoprotein (P-gp)
inhibitors
Mayur C. Yergeri, Manikanta Murahari, L.B. Nitin
Department of Pharmaceutical Chemistry, SVKMs Dr. Bhanuben Nanavati College of Pharmacy, Mumbai,
Maharashtra, India

Multidrug resistance (MDR) of cancer cells is a huge challenge and important cause of chemotherapy
failure. Search of new drug to treat MDR cancer is still a challenge for the scientists. An attempt has been
made to evaluate 2,4-dimethylacridones as chemosensitizers. A series of novel 2,4-dimethyl- N
10
-substituted
acridones with alkyl side chain as propyl and butyl, varying tertiary amine groups at the terminal end of the
alkyl side chain have been synthesized. All compounds have been characterized by spectral analysis (IR,
1
HNMR and Mass). Synthesized compounds were screened against MCF-7, MCF-7/ADR cells. Novel
acridone derivatives were evaluated for their ability to modulate the cytotoxicity of vinblastine in drug-
sensitive MCF-7/ ADR cell lines to correlate the structure and anti-MDR activity among the synthesized
compounds. The modulator tested at their IC
50
values of vinblastine completely against MCF-7/ ADR cells
in the presence of IC
10
of modulators (1-15) lie in the range of 4.10-28.12 nM. The compounds have shown
good cytotoxicity with an IC
50
of 8-20 M. All the compounds have shown significant effect on MCF-7/
ADR cells. The aim of this is study is to correlate the biological activity with the docking scores and to
investigate the mode of the interactions at the binding site of P-gp protein, which might help in further
development of potent P-gp inhibitors. Also to develop a QSAR model to predict the P-gp inhibition
activity. These findings revealed that by increasing the distance between the ring nucleus and the amino
group from three to four carbons increased the anti-proliferative and anti-MDR activity.
Key words: acridone, P-glycoprotein, cytotoxicity, anti-MDR, vinblastine, QSAR


Structural findings of cinnolines as anti-schizophrenic PDE10A inhibitors
through comparative chemometric modeling
Chanchal Mondal, Nilanjan Adhikari, Amit Kumar Halder, Tarun Jha
*

Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical
Technology, P.O. Box-17020, Jadavpur University, Kolkata-700032, India
*
Corresponding author: Tel: +913324572495(o), 09433187443(m), e-mail: t)upharmCyahoo.com

Schizophrenia is a complex psychiatric disorder associated with the distortion of striatopallidal
neurotransmission of central nervous system. Phosphodiesterase10A (PDE10A) plays crucial role in cellular
signaling pathways in schizophrenia. Inhibition of this enzyme may facilitate better treatment of this disease.
2D-QSAR, HQSAR, pharmacophore mapping, molecular docking and 3D-QSAR analyses were performed
on eighty-one cinnoline derivatives having PDE10A inhibitory activity to understand structural and
physicochemical requirements for higher PDE10A inhibitory activity. 2D-QSAR models were developed by
multiple linear regression (MLR) and partial least square (PLS) analyses using both atom based and whole
molecular descriptors. The best model having considerable internal (q
2
= 0.812) and external (R
2
pred
=0.691)
predictabilities demonstrated importance of atom based topological, whole molecular estate indices and 3D
topological indices. The best HQSAR model was also found to be statistically significant (q
2
= 0.664,
R
2
pred
=0.513) and it highlighted some important structural features. PHASE based pharmacophore
hypothesis showed the importance of three hydrogen bond acceptor and one each ring aromatic and
hydrophobic feature for higher activity. 3D-QSAR CoMFA and CoMSIA models were generated on two
different types of alignment procedures (1) pharmacophore (PHASE) based and (2) docking (GLIDE)
based. GLIDE based alignment produced better results for both CoMFA (q
2
= 0.578; R
2
pred
=0.841) and
CoMSIA (q
2
= 0.610; R
2
pred
=0.824). All generated models were compared to each other to reach a concise
decision regarding structural requirements and mechanism of action of the molecules for higher PDE10A
inhibitory activity.



Pharmacophore modelling, molecular docking and virtual screening to Identify Novel
Topoisomerase-I Inhibitors

Sanal Dev,
a
Sunil.R. Dhaneshwar
b
*
a. Department of Pharmaceutical Chemistry, B.V.D.U Poona College of Pharmacy, Pune, Maharashtra,
India.
b. Professor & Chairperson Department of Pharm.Chemistry, Ras Al Khaimah Medical and Health
Sciences University, College of Pharmaceutical Sciences, Ras Al Khaimah, P.O.Box 11172 U.A.E.
Correspondence E-mail: sunil.dhaneshwar@gmail.com



Topoisomerase enzymes are highly expressed in cells which undergo rapid multiplication. Inhibition of this
enzyme represents a potential therapeutic approach for diseases such as cancer. In order to understand the
structure activity correlation of Camptothecin based topoisomerase inhibitor, we have carried out a
combined pharmacophore modelling, 3D-QSAR,molecular docking and virtual screening studies. A five
point pharmacophore was used to derive a predictive atom based 3D-QSAR model. The generated model
had showed good correlation coefficient for training set and test set. It was also validated using enrichment
factor (EF) and goodness of hit score (GH score) and was used for virtual screening of compounds from
zinc drug like database. Docking study of the hits retrieved from virtual screening revealed the binding
affinity of these inhibitors at the active site of topoisomerase-I enzyme. In silico ADME predictions was also
performed. These findings provide a set of guidelines for designing compounds with better topoisomerase-I
inhibitory potential.



DEVELOPMENT AND VALIDATION OF PHARMACOPHORE AND QSAR
MODELS FOR NEURAMINIDASE INHIBITORS

Deepak Kumar Behera
1
, Pabitra Mohan Behera
1
, Laxmikanta Acharya
1
, Anshuman Dixit
2
and Payodhar Padhi
3

1
Centre of Biotechnology, Siksha O Anusandhan University, Bhubaneswar, Odisha, Pin-751030, India
2
Department of Translational Research and Technology Development, Institute of Life Sciences, Nalco Square,
Bhubaneswar, Odisha, PIN-751005, India
3
Hi-Tech Research and Development Centre, Konark Institute of Science and Technology, Techno Park, Jatni,
Bhubaneswar, Odisha, PIN-752050 India
E-mail: Behera.kumar109@gmail.com

The new influenza H1N1 viral stain has emerged by the genetic combination of genes from human, pig and
birds H1N1 virus. The influenza virus is roughly spherical and is enveloped by a lipid membrane. There
are two glycoproteins in this lipid membrane viz. hemagglutinin (HA) which helps in attachment of the viral
strain on the host cell surface and neuraminidase (NA) that is responsible for initiation of viral infection.
Several neuraminidase inhibitors such as Oseltamivir and Zanamivir have been designed that work by
blocking the function of the viral neuraminidase protein. Neuraminidase inhibitor treatment limits the
severity and spread of viral infections.

A total of 147 molecules were used for the current study. The molecules were clustered in 22 groups on the
basis of physicochemical properties and biological activity. One molecule from each cluster is chosen as
training set and 53 pharmacophore models were generated using Phase module of Schrodinger molecular
modeling software. The remaining 125 molecules were kept in the test set. These were divided into three
groups viz. high activity (HA), medium activity (MA) and low activity (LA) group based on observed IC
50

in Cellular PLD2 concentration response assay. These molecules were screened by the generated
pharmacophore models to assess the predictive power of the models. A few models were selected which can
be used for virtual screening of chemical databases for NA inhibitors.

Receptor Chemoprint derived pharmacophore model for development of CAIX
inhibitors
Prakash Amresh, Kundan Kumar, Asimul Islam, Faizan Ahmad, Md. Imtaiyaz Hassan

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi
110025, India. Email: prakashamresh@gmail.com

Carbonic anhydrase IX (CAIX) is an attractive target for anticancer therapy as selectively expressed in
tumor cells. Various CAs inhibitors (sulfonamides/sulfaumates and coumaris) have been reported as
promising anti-cancer agent, showed appreciable affinity and selectivity. Novel chemical scaffolds with
improved pharmacological properties are essential for the development of safe and potent CAIX inhibitors.
Therefore, we have explored the active site residues of CAIX that interacts to inhibitor(s) to design a potent,
specific and novel pharmacophore. Our model has one hydrogen bond donor, three hydrogen bond
acceptors, and two hydrophobic moiety are defined as essential feature for CAIX inhibitors. Virtual
screening of ZINC chemical databases (210
8
compounds) given 1242 hits with pharmacophore fit score
0.95. Test and decoy sets are used to validate the pharmacophore results. Finally, 10 compounds showed an
optimal spatial orientation (G 10 Kcal/mol; Ki 10 nM) and critical interaction with active site residues
His-94, His-119, Glu-106, Thr-199 and Thr-200, are selected as novel leads to CAIX inhibitor. NMA studies
are carried to illustrate the propensity of active site residues. A significant ADMET and TOPKAT score, and
spatial fitting within the active site suggested ZINC03363328, ZINC08828920, ZINC12941947,
ZINC03622539 and ZINC16650541 as a potential lead molecule for the development of CAIX inhibitor.
Keywords: Carbonic anhydrase IX; anticancer therapy; pharmacophore model; virtual screening; CAIX
inhibitors; NMA

'tructure-?ased *esign of ;,2JE In(i)itors as /ovel 1nticancer 1gents
%anohar Suram-
?
, Pa,an (umar %$S
2
, Shamshair Singh
2
, #am8a8u @undla
2
, #a,eendra *ayam--
2

?. *epartment o7 Biotechnology, +a9aharlal $ehru ;echnological 0ni,ersity /ydera8ad, (ukatpally, /ydera8ad 3 P00 0OP,
"ndhra Pradesh, .ndia

2. @)( Bioscience Pri,ate <imited, .n7ormatics3?, Plot $o3C&, %allapur, /ydera8ad G P00 0CM, "ndhra Pradesh, .ndia.

- Presenting "uthor! -- orresponding "uthor! Email: ra,eendra.dayam@g,k8io.com. Ph: F&?3&OMMP&P?42



@lucose #egulated Protein CO 5@#PCO6, also re7erred as Binding .mmunoglo8ulin Protein 5BiP6 or /SP"P, 8elongs to
the /SPC0 7amily and located in the lumen o7 Endoplasmic #eticulum 5E#6. @#PCO plays a central role in E# 7unctions
like protein 7olding, pre,ention o7 aggregating intermediates, targeting mis7olded proteins 7or degradation, a
F2

8inding and controlling the acti,ation o7 E# stress sensors 5.#E?, PE#(, ";FM6. .n nonstressed cells, @#PCO 8inds to E#
transmem8rane sensor proteins PE#(, .#E?, and ";FM and maintains them in an inacti,e 7orm. @#PCO has also 8een
7ound on the cell sur7ace o7 cancer cells 9here it has 8een sho9n to interact 9ith proteins and in,ol,ed in oncogenic
signaling, tumor cell sur,i,al, tumor progression, angiogenesis, metastasis and resistance to chemotherapy. Ihen
un7olded proteins pull @#PCO a9ay 7rom sensors, these path9ays are acti,ated, sending signals to the nucleus to
trigger un7olded protein response 50P#6. onsidering its role in cancer, targeting @#PCO 9ith a small molecule
inhi8itor could pro,ide a mechanism38ased cancer treatment opportunity. Structurally, @#PCO has an $3terminal
";Pase domain 5"B*6 and a 3terminal su8strate 8inding domain 5SB*6, these t9o domains 9ere connected 8y a
linker. ;he 8inding and release o7 peptide su8strate in SB* are coupled to ";P hydrolysis, 9hich cause
con7ormational change in the protein. ;his study aims to design inhi8itors targeting ";P 8inding pocket o7 @#PCO. .n
the present 9ork, structure38ased pharmacophore models are generated 8ased on o8ser,ed key interactions
8et9een @#PCO and co3crystalli2ed su8strate 5";P analogue6. ;he o8ser,ed key interactions 8et9een @#PCO and
";P3analogue are con,erted into '* pharmacophore 7eatures. )alidated '*3pharmacophore models are used to
retrie,e no,el compounds 9ith di,erse chemical sca77olds 7rom small3molecule ,endor and @)(B.> data8ases. ;he
8inding interactions 7or top pharmacophore hits are predicted using co3crystal structure o7 @#PCO 9ith an ";P
analogue. Further 7iltering is per7ormed 8y analy2ing predicted con7ormations and associated 8inding scores. " set
o7 potential 8inders 9as selected 8ased on pharmacophore mapping, analysis o7 8inding interactions, chemical
no,elty, and predicted physicochemical properties. ompound collection and screening processing in progress.

(ey Iords: @#PCO, Structure Based Pharmacophore, /;)S, Endoplasmic #eticulum, 0n7olded Protein #esponse,
>%E@", #apid >,erlay o7 hemical Structures model 5#>S6, @lide.

Predictive in silico modeling studies of diverse ionic liquids towards the inhibition of AChE enzyme of
Electrophorus electricus

,udra /arayan *as and Kunal ,oy$

*rug ;heoretics and hemin7ormatics <a8oratory,*i,ision o7 %edicinal and Pharmaceutical hemistry,
*epartment o7 Pharmaceutical ;echnology, +ada,pur 0ni,ersity, (olkata C00 0'2 5.$*."6
Email: kunalroyNin@yahoo.com! rudra@research.Ld,u.ac.in


hemicals comprise an essential part o7 the industry 7or maneu,ering the ,ast need o7 the li,ing ecosystem. ;he
cherished goal o7 a chemist lies in the design and de,elopment o7 purpose speci7ic superior chemicals 9ith no 5or
limited6 toxicological mani7estations. .onic li:uids are such a group o7 promising no,el chemicals 9ith potential
use7ulness to9ards ,arious industrial applications 8ecause o7 their interesting chemical nature. /o9e,er, these
chemicals do also su77er 7rom the dra98ack o7 ha2ardous outcomes and hence re:uire proper toxicological
assessment 7or 8ecoming the ecologically diligent ones. ;he present study is an attempt o7 in,estigating the
structural 7eatures o7 a 9ide ,ariety o7 2&2 ionic li:uid to9ards their inhi8itory potential o7 "hE en2yme o7
5(ectrophorus e(ectricus through the de,elopment o7 predicti,e regression and classi7ication38ased 1S;# models. Ie
ha,e additionally per7ormed molecular docking studies to explore the structural attri8utes at the "hE en2yme le,el
9hich depicted corro8orating results 9ith the de,eloped 1S;# models. Both the classi7ication and regression38ased
models ha,e 8een de,eloped and extensi,ely ,alidated in consonance 9ith the proposed >E* guidelines and
encouraging results 9ere o8tained. ;he cations o7 the ionic li:uids 9ere o8ser,ed to 8e more contri8uting to9ards
toxicity. /ydrophilicity as a count o7 /38ond acceptorDdonor measures, hydropho8icity as re7lected in the E;" index
DE
B
, 8ranching depicted 8y the connecti,ity measure
?
F
v
and E;" index J5GH6
T
DGHK, and positi,ely charged 43species
as sho9n 8y the ,aria8les AtypeI4I1J and SIssss4 9ere o8ser,ed to 8e maLor contri8utors.

;he docking studies
chie7ly portrayed the pi 5X63cationic type interaction o7 the cationic $
F
atom 9ith the Phe
2OO
, Phe
2&0
and ;rp
2'

residues present in the acyl 8inding pocket.


Pharmacophore Modelling and Virtual screening for JAK3 Inhibitors



M. Rajeswari, N Santhi, R Ashwini and M Kirithika

Department of Biochemistry, Biotechnology & Bioinformatics Avinashilingam
Institute for Home Science and Higher Education for Women
Coimbatore-641043, Tamil Nadu.


The Janus Kinases (JAKs) are family of non-receptor tyrosine kinase consisting of JAK1, JAK2,
JAK3 and TYK2 which are activated after cytokine receptor activation. Among the JAK family, JAK3 is
abundantly expressed in hemopoietic cells and plays an important role in normal lymphocyte development
and function. Therefore selective targeting of JAK3 may have therapeutic benefit over broader JAK
signaling inhibition for the treatment in various areas namely oncology, organ transplantation, and
autoimmune diseases.

In the present study, pharmacophore model was generated for Human Janus Kinase 3 inhibitors
utilizing the Phase module of Schrodinger software. Subsequently atom based 3D-QSAR model was
obtained and database screening was used in the search of novel lead compounds. The lead compounds were
then docked with JAK3 to study the interaction of inhibitors with the protein.

A total of 116 JAK3 inhibitors/compounds with IC
50
value were collected from the literature and
pIC50 value was calculated. The dataset contain different chemical classes namely phenyl aminoprymidines,
N-phenylmethanesulfonamide, nitrile carboxamide, N-cyanomethylbenzamide, 2 aminoethylketone, 2-
Benzimidazolyl-9-(chroman-4-yl)-purinone, di-substituted pyrimidine, trisubstituted pyrimidine and 5H-
pyrrolo(2,3-b) pyrazine-2-phenyl ethers. A four point pharmacophore model was developed. Out of 14
models, AAHR.92 has the highest correlation coefficient (0.9422). The collected 116 compounds were
ranked based on the pIC
50
value. Out of 116 compounds, 20 compounds were chosen as test set (every 5
th

compounds from the ranked list) and the remaining 96 were selected as training set to generate atom-based
QSAR models. The model generated has Q
2
value of 0.6023 indicating the developed model is a good one.
Then AAHR.92 was used as 3D query to screen databases viz. NCI, Maybridge, and Asinex. From that 1200
hits were got and further filtered based on the Lipinskis rule of five and molecular docking using JAK3
protein (4HVD). Among 1200 hits 10 hits showed better docking score (ranging from -7.0 to -10.0) and
interaction with JAK3. These molecules will be further experimentally validated to design inhibitors for
JAK3.






SAR, Pharmacophore and Molecular Docking Studies of Aromatase
Inhibitors for Therapeutic Application in Post-menopausal Diseases
Minesh Jethva, Chetan Malondkar, Govardhan Anande, Sagar Bhalgat and Md Ataul Islam
*

Department of Bioinformatics
Rajiv Gandhi Institute of Information Technology and Biotechnology
Bharati Vidyapeeth Deemed University, Pune-Satara Road, Pune 411 043
Email: ataul.islam80@gmail.com


High estrogen levels blamed for a wide range of distressing symptoms including cardiovascular diseases,
ovarian cancer and breast cancer. Estrogens are a group of compounds named for their importance in both
menstrual and estrous reproductive cycles. Aromatase is an enzyme responsible for a key step in the
biosynthesis of estrogens and target for the design of inhibitor in the treatment of hormone dependent breast
cancer for postmenopausal women. Drug discovery and development process is a complex along with very
time and resource consuming method. Chemometric drug discovery process is combined with chemical and
biological spaces in order to streamline drug discovery, design, development and optimization of the
molecule. Quantitative structure activity relationship (QSAR) established trend of changing biological
activity with chemical structure whereas, pharmacophore model gives three dimensional orientations of
important pharmacophoric features for binding at the active site cavity. In molecular docking method, ligand
interacts to the protein or nucleic acid target and provides a conceptual frame work for designing the desired
potency and specificity of potential drug leads for a given therapeutic target.
In the present study, a set of 59 aromatase inhibitors have been considered for QSAR, pharmacophore and
molecular docking studies using Schrodinger2013. The whole data set is randomly divided into training (n
tr

= 39) and test (n
ts
= 20) set for model generation and validation of derived model respectively. The QSAR
study (R
2
= 0.764, SD = 0.540 Q
2
= 0.707, Pearson R= 0.842 and RMSE = 0.553) explained that aromatic
and hetero-aromatic along with topological descriptors are important for inhibitory concentration. The
pharmacophore study (R
2
= 0.748, SD = 0.483 Q
2
= 0.896, Pearson R = 0.982 and RMSE = 0.173) revealed
with importance of hydrophobicity and aromatic ring features and suggest that high hydrophobicity might be
crucial for inhibition at the active site. Molecular docking of whole dataset gives significant GlideScore,
where most active compounds obtained -8.085 and least active -4.334.

















2(armacop(ore *evelopment for 2-;lycoprotein 1ctivators and ;eneration of lead from /atural 2roducts for
Improved K-amyloid clearance in 1lz(eimerLs disease3
A&ravin Shin%e, 4ikhi( Vi%yasa,ar*, Sivakami Dhu(ap
'SI29Unit for 2esearch an% Deve(opment of Information &ro%ucts
Y+opasanaY, OPD?, Paud #oad, (othrud, Pune 3 4??0'O. .ndia, nikhi(.vi%yasa,arCur%ip.res.in


P-glycoprotein (Pgp) belongs to the ATP binding cassette (ABC) transporter family, which are important
constituents of the blood-brain barrier (BBB), blood-cerebrospinal fluid (B-CSF), and the bloodtestis
barrier (BTB).
Pgp is a protein involved in the active transport of molecules across biological membranes, and it has been
shown that alterations of its expression and/or activity are related to the onset of neurodegenerative
disorders. Indeed, it has been reported that up-regulation of this efflux pump is responsible for a decrease in
-amyloid intracellular accumulation, which is an important hallmark in AD. Therefore, targeting -amyloid
clearance by Pgp stimulation could be an useful strategy to prevent AD progression.
Present work aims to highlight a ligand based pharmacophore modelling primarily using the information
from scientific as well as patent art. A diverse set of molecules belonging to oleocanthal, benzopyrane,
benzothiazole derivatives and tetrahydroisoquinoline derivative were considered for the generation of a
common pharmacophore model.
The best pharmacophore model generated consisted of a four point pharmacophore with one hydrogen bond
acceptor (A), one lipophilic/hydrophobic group (H) and two aromatic rings (R). The pharmacophore
developed was used as a 3D query for screening novel Pgp activators using a natural product database
developed in-house. The hits were further optimized by applying ADME filters followed by molecular
docking studies against the 3D structure of Pgp. These compounds may serve as scaffolds for further
development of natural product based selective Pgp activators.

First Report on Exploring Structural Requirements for a Class of Nucleoside Inhibitors
(PfdUTPase) as Antimalarials: QSAR, Pharmacophore Mapping and Multiple Docking
Studies
Probir Kumar Ojha and Kunal Roy
Jadavpur University Kolkata

Drug Theoretics and Cheminformatics Laboratory, Division of Medicinal and Pharmaceutical Chemistry,
Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032 (India), Email:
probirojha@yahoo.co.in; kunalroy_in@yahoo.com


Multi-drug resistance to the available antimalarial drugs is a major threat for malaria treatment. Due to the
recent characterization of human and parasite genome sequences, both ligand and target based drug design
strategies may be helpful for the design of potential antimalarial compounds with reduced degree of
resistance. The present work deals with quantitative structure-activity relationship (QSAR) modeling,
pharmacophore mapping and multiple docking studies of a series of 95 nucleoside analogs as inhibitors of
Plasmodium falciparum deoxyuridine-5-triphosphate nucleotidohydrolase (PfdUTPase) enzyme involved in
nucleotide metabolism. The QSAR and pharmacophore models were validated both internally and externally
showing good statistical results. The docking study was performed and validated using three different
software tools namely Discovery Studio 2.1 (Accelrys), Maestro 9.3 (Schrodinger) and MOE (Chemical
Computing Group). The QSAR studies revealed that compounds containing substituted aromatic carbons
(aasC fragment) and those bearing -OH groups without an n-oxolane ring exert potent PfdUTPase inhibitory
activity. The best pharmacophore hypothesis (hypothesis 1) possessed four features: (i) one hydrogen bond
donor (HBD), (ii) one hydrogen bond acceptor (HBA), (iii) one hydrophobic (HYD) and (iv) one ring
aromatic (RA) features. The docking studies revealed that the PfdUTPase inhibitors interact with a pocket
containing Phe46, Lys48, Leu88, Asn103, Gly106, Leu107, Ile108, Tyr112, Ile116, Ile117, Ala118 and
Ala119 amino acid residues. The interaction pattern of all the PfdUTPase inhibitors was almost same in case
of docking using Discovery Studio 2.1 (LigandFit), Maestro 9.3 (Glide) and MOE software. This work thus
presents the first QSAR report for nucleoside analogs which may serve as an efficient tool to address the
increasing threat of malaria in the developing countries.







3D-QSAR and molecular docking studies of ureido-substituted benzene sulfonamides
as anti-tubercular agents

Rahul P. Gangwal,
a
Vivek Neekhra,
a
Kanchan Khandelwal,
a
Manisha Lalit,
a
Mangesh V. Damre,
a
Abhay T.
Sangamwar
a,
*

a
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sect-67,
S.A.S. Nagar, Punjab-160 062, India, * Corresponding author: E-mail: abhays@niper.ac.in

-carbonic anhydrase (mtCA1) is an enzyme which catalyzes reversible hydration of carbon dioxide to generate
bicarbonate and a proton. It is an essential enzyme for survival of Mycobacterium tuberculosis in starvation. This
finding supports the development of -carbonic anhydrase inhibitors as new potential anti-tubercular agents. Herein,
we have performed 3D-QSAR and molecular docking analysis on novel series of ureido-substituted benzene
sulfonamides to design potent -carbonic anhydrase inhibitors. This study correlates the -carbonic anhydrase
inhibitory activities of 28 benzene sulfonamides to several stereo-chemical parameters representing steric,
electrostatic, hydrophobic, hydrogen bond donor and acceptor fields. The developed CoMFA and CoMSIA models
have exhibited excellent r
nc
2
values of 0.996 and 0.987, and r
c
2
values of 0.739 and 0.498, respectively. The
developed CoMFA and CoMSIA models were validated by test set and Y-randomization method, which shows that
predicted values are in good agreement with experimental values. The binding mode of sulfonamides at the active site
of -carbonic anhydrase was explored by Glide (5.5). We have accordingly designed novel -carbonic anhydrase
inhibitors by utilizing the LeapFrog and predicted with excellent activity in the developed models.
Keywords: -carbonic anhydrases; CoMFA; CoMSIA; mtCA1; Molecular docking: Sulfonamides.







Pharmacophore based Identification of Inhibitors against RNA polymerase of Drug
Resistant Mycobacterium tuberculosis
Vipin Menon A, Sanjay kumar

S., Waheeta Hopper

Department of Bioinformatics, School of Bioengineering, Faculty of Engineering and Technology, SRM
University, Kattankulathur, Tamil Nadu, India.


The increase in the prevalence of drug resistant strains of Mycobacterium tuberculosis is the leading cause
for treatment failures in the clinical settings. Rifampin, an effective first line drug, inhibits the RNA
polymerase -subunit (encoded by rpoB gene) in M. tuberculosis. However, rifampin drug resistance is a
major problem in developing countries. Rifampin resistance strains arise due to the mutation occurring in
active site region of rpoB gene. The aim of the present study is to identify novel inhibitors of the mutated
rpoB gene. Using I-TASSER protein modeling server, both wild and mutant type of RNA polymerase -
subunit were modeled. Using site map, rifampin binding site was identified for wild and mutant type of
RNA polymerase -subunit. Identification of novel compounds was carried out using Schrodingers Phase
ligand based pharmacophore screening against mutant RNA polymerase -subunit. The compounds having
similar pharmacophore features were subjected to high throughput virtual screening against mutant RNA
polymerase -subunit. Ligands with maximum Glide XP score were shortlisted. Novel compounds were
identified using the interaction with the mutated RNA polymerase -subunit. In this study, we have
identified a set of novel compounds as drug leads for Rifampin drug resistant M. tuberculosis.

Keywords: Mycobacterium tuberculosis, Drug resistance, Rifampin, RNA polymerase -subunit



Multi-Target-Directed Identification for Novel Lead Candidates against Trypanosoma
and Leishmania Glycogen Synthase Kinase3

Shagun Krishna, Nidhi and Mohammad Imran Siddiqi
Molecular and Structural Biology Division, CSIR - Central Drug Research Institute, Lucknow 226 031, India


Human African trypanosomiasis (HAT) and Leishmaniasis, affects so many people worldwide. Both
diseases are vector born, transmitted by the bite of an insect. Trypanosoma brucei, the causative agent of
Human African Trypanosomiasis (HAT), and Leishmania donovani causative agent of leishmaniasis
expresses two proteins designated as GSK-3 short and GSK-3 long. Biological evidence that GSK-3 short
enzyme could be a potential target for anti-leishmanial drug development was recently described for
L.donovani and for T.brucei as well. Trypanosoma brucei GSK-3 (TbruGSK-3) short and Leishmania
donovani GSK-3 short (LdGSK-3) have 65 % amino acid sequence identity. We have presented a computer-
assisted strategy to screen for multi target inhibitors using a combination of molecular docking and ligand
based pharmacophore study. In this present study, we employed a ligand based pharmacophore approach
constructed with already known selective inhibitors
1, 2
, followed by in silico screening of Maybridge
database. Selected top scoring compounds were docked in the homology model of Tbru and Ld GSK-3 to
identify new inhibitors that may help in design of potent and selective common GSK-3 inhibitors for both
the species. In conclusion; we exploited the CADD methodology for the generation of novel multitarget
inhibitors of GSK3 targeting two species of important human pathogens.









Molecular modelling study of PPAR ligands for the therapeutic application
in the treatment of Type-2 diabetes

Shipra Raturi, Sailee Bendre, Farahdeeba Sheikh, Pritee Chunarkar and Md Ataul Islam
*
Department of
Bioinformatics, Rajiv Gandhi Institute of Information Technology and BiotechnologyBharati Vidyapeeth
Deemed University, Pune-Satara Road, Pune 411 043Email: ataul.islam80@gmail.com
;ype32 dia8etes is characteri2ed 8y relati,ely lo9er le,els o7 insulin, much needed 7or glucose meta8olism and thus
e77ecting 8ody=s a8ility o7 turning 7ood into energy. onspiring to produce a 9orld9ide epidemic ;ype32 dia8etes
solely accounts 7or more than &0R o7 the total dia8etes, ha,ing o8esity as the single most important contri8utor to
its pathogenesis. .ts therapy mainly relies on approaches pertaining to receptor agonists 9hich aim on enhancing the
insulin action. ;hese agonists mainly peroximsome proli7erator acti,ated receptor G Z 5PP"#3Z6 9ith their pre,alent
expression in the adipose tissues, ha,e pro,ed to 8e an e77ecti,e means to decrease insulin resistance. ;he PP"#3Z is
a mem8er o7 nuclear hormone receptor super7amily and 9ork as ligand acti,ated transcription 7actors and control
the expression o7 genes in,ol,ed in lipid, lipoprotein and glucose meta8olism. "ccordingly, acti,ating these receptors
has 8ecome a promising therapeutic strategy 7or designing drugs against the disease. ;he lead, 7rom posing the
a7orementioned agonists as potent links, to deri,ing signi7icantly promising drugs against the disease o7 interest, is
landmarked 8y ,arious computational approaches including structural 8ioin7ormatics, pharmocophore ,1S"# and
molecular docking. .n the present study, pharmacophore, :uantitati,e structure acti,ity relationship 51S"#6 and
molecular docking studies are per7ormed to optimi2e potent and less toxic PP"#3Z 7or therapeutic application in
type32 dia8etes. Pharmacophore is a set o7 7unctional group in a spatial arrangement that represents the interaction
made common 8y a set o7 small molecular ligands 9ith a protein receptor. ;he aim is to ensure good co,erage o7
con7ormational space 9ith the minimum num8er o7 con7ormers. 1S"# attempts to 7ind consistent relationship
8et9een 8iological acti,ity and molecular properties on the 8asis o7 structural key 7eatures. .n molecular docking,
ligand interacts to the receptor molecule and pro,ides a conceptual 7rame 9ork 7or designing the desired potency
and speci7icity o7 potential drug leads 7or a gi,en therapeutic target..n the present 9ork, a set o7 P& compounds o7
PP"#3Z ha,e 8een considered 7or 1S"#, pharmacophore and molecular docking studies. ;he 9hole data has 8een
randomly di,ided into training 5n
tr
S406 and test 5n
ts
S?&6 sets 7or model generation and ,alidation o7 generated model
respecti,ely. ;he 1S"# model 52
?
S 0.C0O, K
?
S 0.C2?, se S 0.''P, 2
?
pre%
S 0.MMC6, de,eloped 9ith the importance o7
dipole moment, or8ital energy, chirality and rigidity o7 the molecule. ;he pharmacophore model o8tained 9ith the
importance o7 hydrogen 8ond 5/B6 acceptor and donor along 9ith ring aromatic and hydropho8icity o7 the molecule.
;he good statistical parameters 52
?
S0.&20, S* S 0.400, K
?
S0.OO0, &earson 2 S 0.&C?, 2MS5 S 0.MP06 o7 the
pharmacophore model suggests superiority o7 the model selection. ;he molecular docking study success7ully
correlates the 7unctionality de,eloped in pharmacophore and 1S"# study.










Exploring QSTR modeling and toxicophore mapping for
identification of important molecular features contributing to the
chemical toxicity in Escherichia coli


Subrata Pramanik and Kunal Roy*
Drug Theoretics and Cheminformatics Laboratory,
Division of Medicinal and Pharmaceutical Chemistry,
Department of Pharmaceutical Technology,
Jadavpur University, Kolkata 700 032 (INDIA)
Email: kunalroy_in@yahoo.com; kroy@pharma.jdvu.ac.in
URL: http://sites.google.com/site/kunalroyindia/




Biodiversity deprivation can affect functions and services of the ecosystem. Changes in biodiversity alter
ecosystem processes and change the resilience of ecosystems to ecological changes. Bacterial communities
are the main form of biomass in the ecosystem and one of largest populations on the planet. Bacterial
communities provide important services to biodiversity. They break down pollutants, municipal waste and
ingested food, and they are the primary route for recycling of organic matter to plants and other autotrophs,
conversion of inorganic matter into new biological tissue using sunlight, management of energy crisis
through use of biofuel. In the present study, computational chemistry and statistical modeling have been
used to develop mathematical equations which can be applied to calculate toxicity of new/unknown
chemicals/biofuels/metabolites in Escherichia coli. 2D and 3D descriptors were generated from molecular
structure of compounds and mathematical models have been developed using genetic function
approximation followed by multiple linear regression (GFA-MLR) method. Model validity was checked
through defined internal (R
2
=0.751 and Q
2
=0.711), and external (R
2
pred
=0.773) statistical parameters.
Molecular features responsible for toxicity were also assessed through 3D toxicophore study. The
toxicophore-based model was validated (R= 0.785) using qualitative statistical metrics and randomization
test (Fischer validation).


Keywords: Biodiversity; Escherichia coli; QSTR; Chemical toxicity; Statistical modeling; toxicophore


Chemometric studies of phamarcophore, QSAR and molecular docking of
Catechol Diethers as potent Anti-reverse transcriptase agents

Sumeet R. Deshmukh, Neha Kulkarni, Supriya Kulkarni, Pritee Chunarkar and Md Ataul Islam
*
Department of Bioinformatics
Rajiv Gandhi Institute of Information Technology and Biotechnology
Bharati Vidyapeeth Deemed University, Pune-Satara Road, Pune 411 043
Email: ataul.islam80@gmail.com


Natural products are important sources of drug discovery. In this context groups of different set of chemical
compound were taken and its pharmacophore model and Qsar study (R = 0.691, S.D. = 0.540, Q = 0. 680,
Pearson R = 0.860, RMSE = 0.530) were carried, the model suggests that 3D orientation of the
pharmacophoric features and inter-feature distances are prime biophore for inhibition at the active site cavity
and the model docked into the different cavities of the reverse transcriptase (PDB ID: 1REV) of human
immunodeficiency virus (HIV) and results were discussed. The molecular docking is performed and
significant GlideScore are obtained. The most active and least active molecules in the dataset give glidescore
of -11.643 and -5.423 respectively. Binding interactions observed between the catalytic residues at the active
cavity and most active ligand also successfully correlate the functionalities developed in the pharmacophore
study. Hence, considering the facts those compounds can be used effectively for HIV-1 drug discovery.





Pharmacophore Exploration of HIV-1 Protease (PR) Inhibitors
Using Chemometric Techniques

Shweta Sonar, Vishakha Nair and Md Ataul Islam
*
*epartment o7 Bioin7ormatics

#aLi, @andhi .nstitute o7 .n7ormation ;echnology and Biotechnology, Bharati
)idyapeeth *eemed 0ni,ersity, Pune3Satara #oad, Pune G 4?? 04' Email: ataul.islam80@gmail.com


The HIV-1 Protease (PR) hydrolyzes viral poly-proteins into functional protein products that are essential for viral
assembly and subsequent activity and it also an obligatory enzyme in the replication process of the HIV virus. The
abundance of structural information on HIV-1PR has made the enzyme an attractive target for chemometric drug
design strategies.
In the present work, a data set of 43 compounds of HIV-1 protease inhibitors are considered for chemometric study
using Schrodinger2013 package to find out important molecular functionalities those are crucial for biological activity.
Quantitative structure activity relationship (QSAR) gives the importance of fields and functionalities whereas
pharmacophore space modeling tells about 3D orientation of crucial functional groups which might be favorable for
binding at the active site cavity. Molecular docking predicts the favorable orientation of the ligand to fit at the active
site of the receptor molecule whereas virtual screening provides probable lead molecules based of the generated
models.
In the present study, the pharmacophore model (R = 0.871, S.D. = 0.582, Q = 0. 813, Pearson R = 0.976, RMSE =
0.576) developed with importance of hydrogen bond (HB) acceptor and aromatic ring features. The model suggests
that 3D orientation of the pharmacophoric features and inter-feature distances are prime biophore for inhibition at the
active site cavity. The high Pearson R value indicates the superiority of selected model. The molecular docking is
performed and significant GlideScore are obtained. The most active and least active molecules in the dataset give
glidescore of -9.003 and -6.423 respectively. Binding interactions observed between the catalytic residues at the active
cavity and most active ligand also successfully correlate the functionalities developed in the pharmacophore study.






Patinformatics as a complimentary tool for the virtual screening of selective CDK2
inhibitors

Abhijeet.Dhulap, Sivakami.D, R.R.Hirwani
CSIR-Unit for Research and Development of Information Products (URDIP)
Pune, India


In India, cancer has been known since ancient times and this has been mentioned in the ancient Ayurvedic
books like Charak Sanhita, Madhav Nidan, Sushrut Sanhita and Arka Prakash. Natural products play a
dominant role in cancer chemotherapeutics with more than 70% of anticancer compounds being either
natural products or derived from natural products.

Till today many medicinal plants have been screened for their activity on the basis of
ethanopharmacology on random basis. The Indian Territory has an extensive indigenous
collection of natural product remedies for treating cancer and various other diseases.
Such natural product scaffolds can not only be used for the treatment of cancer but
also for the development of new lead molecules.

The drug discovery process starts from the selection of target enzyme. The drug molecule interacts with
target enzyme and inhibits it. In major cases of cancer treatment the cell regulator enzymes are target
enzymes. A family of conserved serine/threonine kinase known as cyclin-dependent kinases (CDKs) drives
orderly cell cycle progression in eukaryotic cell. CDKs provide a promising target for diagnostic
characterization of malignancies and development of novel therapeutic interventions. There are 11
members of the CDK family known till now. Among these, CDK 1, 2, 3, 4, and 6 are known to play
important roles in the cell cycle
.
CDK2 activity is necessary for normal mammalian cell cycle progression
and it is suggested that CDK2 might be a useful therapeutic target for treating cancer.

This poster firstly aims to highlight the application of Patinformatics firstly to create a database containing
therapeutically active natural products and then using this information for modeling pharmacophore which
in turn is used as an input for the virtual screening of natural products which show activity against cancer;
particularly compounds which show selective CDK-2 inhibition.


Quantitative structure activity relationship studies on Eugenol derivatives/analogs for
antifungal activity against Candida

Himanshu Tripathi
1
, Komal Kalani
2
, Suaib Luqman
3
, Santosh K. Srivastava
2
, Feroz Khan
1
*
1
Department of Metabolic & Structural Biology,
2
Analytical Chemistry Department,
3
Department of
Molecular Bioprospection, CSIR-Central Institute of Medicinal & Aromatic Plants, Lucknow - 226015,
India, * Correspondence: f.khan@cimap.res.in


A quantitative structure activity relationship (QSAR) studies was performed on eugenol derivatives/analogs
for antifungal activity. A total of 28 active antifungal compounds/drugs were used in the training set for the
development of QSAR model so that to predict the activity against Candida albicans. We have calculated
initially 52 chemical descriptors for each compound in the training set. Various descriptors like electronic,
steric and thermodynamic were calculated by the Scigress Explorer software (Fujitsu, Poland). The QSAR
model was developed by forward stepwise multiple linear regression approach using leave one out (LOO)
validation method. The developed QSAR model showed significant regression coefficient (r
2
=

0.8) and
cross validation regression coefficient (rCV
2
=0.72) that reflects a fair 72% predictive accuracy. QSAR
model regression equation showed only two chemical descriptors viz., shape index (basic kappa, order 3)
and methyl group count, which are well correlated with the antifungal activity of training set active
compounds/drugs. Later, we have screened novel designed compounds/derivatives through derived QSAR
model. Predicted active compounds/derivatives showed significant binding affinity on antifungal targets
through docking studies. Potential lead compounds showed compliance with electronic parameters of drug
likeness and ADMET. The present study will be a useful tool for screening and identification of eugenol
derivatives/analogs or similar pharmacophore containing compound for antifungal activity against Candida.
Keywords: Eugenol, Caffeic acid, QSAR, Docking, Drug likeness, ADMET, Candida albicans, antifungal activity.


Structure Based Subsite Informed Pharmacophore Generation and its Applications to
Virtual Screening of Dipeptidyl Peptidase IV (DPP-IV) Inhibitors
Jagatkumar Upadhyay
1
, Anuradha Gajjar
2
, B.N. Suhagia
1
1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Dharmsinh Desai University, Nadiad,
Gujarat, jagat7685@gmail.com
2
.Ramanbhai Patel College of Pharmacy, CHARUSAT, Changa, Gujarat,


In the long process of drug discovery program, virtual screening is a gestation period in which conceiving
right hits is the bright future for developing drug candidate. A detailed understanding and critical analysis of
every available structural information is indispensable for the development of virtual screening protocol.
Various DPP-IV inhibitors have been approved in recent years for the management of type-2-diabetes. DPP-
IV inhibition tends to increase with increase in number of binding sites. The aim of the present study was to
design inhibitors which bind to a specific subsite of DPP-IV and thereby inhibit it. Here we present the
subsite analysis of DPP-IV crystal and different pharmacophore were derived using Phase, 3.5, Schrodinger
Software Inc., and run against commercial compound libraries. Prior to pharmacophore screening, database
was prepared using filters for drug-likeness. The hits obtained from the Pharmacophore screening were
docked in DPP-IV crystal structure using GLIDE docking, 5.9, Schrodinger Software Inc. Docked poses of
compounds were scored using Glidescore and compounds were ranked and clustered. Top-ranked subsite
specific hits from each Pharmacophore search are reported here along with their binding mode information.
These compounds may bind to specific subsite in DPP-IV and serve hits for lead identification program.



Development of Energetic Pharmacophore for the designing of 3-phenyl-1-(4-(2-(piperidin-1-
yl)ethoxy)phenyl)prop-2-en-1-one Derivatives as Selective ER- Inhibitors

Pritam N. Dube, Sameer I. Shaikh, Santosh N. Mokale*
Department of Pharmaceutical Chemistry, Y. B. Chavan College of Pharmacy, Aurangabad-431001, Maharashtra,
India, *Corresponding Author: santoshmokale@rediffmail.com

Background: The natural and synthetic analogs of chalcones have been reported to exhibit antineoplastic,
antiallergic, antihepatoprotective, and estrogenic activity. Herein, we report substituted chalcones as a new
class of compounds that exhibit selectivity for ER- binding along with antiproliferative and cytotoxic
activity on human breast cancer cell line. The energetic pharmacophore (E-pharmacophore) features were
generated and ranked using energetic terms of Glide XP docking for chalcone scaffold to optimize its
structural requirement for ER- inhibition.
Materials and Methods: Molecular Docking Studies were performed in Maestro 9.3 using Glide v5.8. The
energetic pharmacophoric hypothesis was generated using E-pharmacophores script of docking post-
processing script center in Maestro. This script uses Phase v3.4 to initially generate the pharmacophoric sites
using default set of six chemical features: hydrogen bond acceptor (A), hydrogen bond donor (D),
hydrophobic group (H), negatively charged group (N), positively charged group (P), and aromatic ring (R).
Hydrogen bond acceptor sites were represented as vectors along the hydrogen bond axis in accordance with
the hybridization of the acceptor atom. On the basis of generated pharmacophore, the new 4-phenyl-6-(4-(2-
(piperidin-1-yl)ethoxy)phenyl)-4,5-dihydropyrimidin-2-amine and 5-phenyl-3-(4-(2-(piperidin-1-
yl)ethoxy)phenyl)isoxazole derivatives were synthesized. The synthesized compounds were screened for
human breast cancer activity.
Result: The overall study helped us to design new 3-phenyl-1-(4-(2-(piperidin-1-yl)ethoxy)phenyl)prop-2-
en-1-one analogues by modification of our previously synthesized compounds. It was found from docking
study and E-pharmacophore features score that hydrogen bond acceptor or donor in compounds was
important for binding to ER-. The newly sunthesized analogues shows better potency than previous one.
Conclusion: The docking study and generated features by E-pharmacophor were used to design the new
compounds. The twenty compounds were synthesized from which six compound posses potent anticancer
activity. Further, the development of E-pharmacophore is a useful method for design of new compounds and
can be applied for screening of compounds.

PHASE-BASED PHARMACOPHORE MODEL GENERATION AND 3D-DATABASE
SEARCHING FOR NOVEL AND POTENTIAL 5-HT
6
ANTAGONISTS
V. S. Velingkar, C. Anil
Department of Pharmaceutical Chemistry, Principal K. M. Kundnani College of Pharmacy, Jote Joy Building, Rambhau
Salgaonkar Marg, Cuffe Parade, Mumbai-400 005, India.

5-HT
6
antagonism has been proposed on a promising approach for treating cognitive impairment
associated with neuropsychiatric disorders

(e.g. Alzheimers disease, Schizophrenia). Using the programme
PHASE,

herein described is pharmacophore generation and atom-based 3D-QSAR analysis

of previously
reported Aryl Sulphonamide and Sulfone based 5-HT
6
antagonists in order to get insight into their structural
requirements responsible for high affinity.
The best pharmacophore model generated consisted of four features AAPR. Based on model
generated, a statistically valid 3D-QSAR with good predictability was developed, its statistical values by
PLS as R
2
=0.9848, SD=0.1402, F=281.5, P=2.283e-22, Q
2
=0.6714, RMSE=0.3864, Pearson-R=0.8308.
Derived pharmacophore was used as a query to search designed novel database. Hits retrieved were studied
progressively through comparing their fitness score and predicted activity. The best hits present new
scaffolds with a potential for 5-HT
6
antagonism.
Thus the established computational tool endowed with high predictive ability and robustness which
might be useful for the design and optimization of new 5-HT
6
antagonists.



Ligand based design, synthesis and CoMSIA studies of new diphenylamine containing 1,2,4-triazoles
as potential anti-TB agents

Bharathkumar Inturi
*
, Mohan Krishna K, Gurubasavaraj V Pujar

Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysore-570015,
Karnataka, India.


A new series of 4-(arylideneamino)-2-(substituted-aminomethyl)-5-[2(2,6,dichlorophenyl amino)benzyl]-2H-1,2,4-
triazole-3(4H)-thiones 4a-l, 3-{3-[2-(2,6-dichlorophenyl amino)benzyl]-5-mercapto-4H-1,2,4-triazol-4yl}-2-
arylthiazolidin-4-ones 5a-f and 2-(2-(2,6-dichllorphenylamino)benzyl)-3-(arylideneamino)-[1,2,4] triazolo [5,1-
b]quinazolin-9(3H)-ones 6a-f were synthesized from 4-arylideneamino-5-[2-(2,6dichlorophenylamino) benzyl]-2H-
1,2,4-triazole-3(4H)-thiones 4a-f. All the synthesized compounds were characterized by physicochemical, spectral
(IR,
13
CNMR,
1
HNMR and MASS) and elemental analysis data. The synthesized compounds were screened for in-
vitro antimycobacterial potential by standard Microplate Alamar Blue Assay (MABA) and serial dilution method
against Mycobacterium tuberculosis H
37
Rv and in-vitro antibacterial activity. The synthesized compounds 4a, 4e and
4d have shown potential activity against M. tuberculosis H
37
Rv strain with MIC of 0.2, 0.4 and 3.13 M respectively.
To investigate the SAR of diphenylamine containing 1,2,4-triazole derivatives in more details, CoMSIA(q
2
-0.511, r
2
-
0.953) models on Mycobacterium tuberculosis H
37
Rv were established by using SYBYL X. 2.0. The effects of
different global molecular descriptors were studied including lipophilicity (cLogP), polar surface area (PSA), and
steric bulk (CMR) on model predictivity. Incorporation of polar surface area (PSA) descriptors into the models had
significant effects on model predictivity. The generated 3D-QSAR models can be used for further rational design of
novel diphenylamine containing 1,2,4-triazoles as potent antitubercular agents.

KEY WORDS: 1,2,4-triazoles, Mycobacterium tuberculosis, MABA assay, 3D-QSAR, CoMFA, CoMSIA, triclosan



Pharmacophore Generation and Atom-based 3D-QSAR of 3-pyridyl
Derivatives as DPP-4 Inhibitors.
Patel Bhumika, Ghate Manjunath
Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, SG Highway,
Ahmedabad

Background: Dipeptidyl peptidase IV (DPP IV) deactivates the natural hypoglycaemic incretin hormone
GLP-1. Inhibition of this enzyme restores glucose homeostasis in diabetic patients making it an attractive
target for the development of new antidiabetic drugs. Herein, we describe the development of effective and
robust pharmacophore model and the structureactivity relationship studies of 34 3-pyridyl acetic
acid/acetamide derivatives previously reported for DPP-4 inhibition
1,2
using Phase module of Schrodinger
2013.

Results: A 4-point pharmacophore model was developed and the generated pharmacophore model was used
to derive a predictive atom-based 3D quantitative structureactivity relationship analysis (3D-QSAR) model
for the studied dataset. The obtained 3D-QSAR model has an acceptable correlation coefficient value (r
2
=
0.85) along with good statistical significance as shown by high Fisher ratio (F = 103.6). The model also
exhibited good predictive power confirmed by the high value of cross validated correlation coefficient and
r
2
pred
(q
2
= 0.53, r
2
pred
= 0.66). Further, pharmacophoric model was employed for virtual screening to identify
potential DPP-4 inhibitors.

Conclusions: The QSAR model suggests that H bond donor character of terminal amino group at 5
th

position, electron withdrawing character of various substituted acetic acid/acetamide group at terminal end
of 3
rd
position is crucial for the DPP-4 inhibitory activity while positively ionic group at 5
th
position
negatively contribute to the DPP-4 inhibition. These findings provide a set of guidelines for designing
compounds with better DPP-4 inhibitory potential.
Keywords: Diabetes, DPP-4, 3-pyridyl derivatives, Pharmacophore, 3D-QSAR
References:
1. Miyamoto, Y. et al. Discovery of a 3-pyridylacetic acid derivative (TAK-100) as a potent, selective and
orally active dipeptidyl peptidase IV (DPP-4) inhibitor. J. Med. Chem. 2011, 54, 831850
2. Miyamoto, Y. et al. Design and synthesis of 3-pyridylacetamide derivatives as dipeptidyl peptidase IV
(DPP-4) inhibitors targeting a bidentate interaction with Arg125. Bio Med Chem. 2011, 19, 172185
Acknowledgement: We sincerely thank Schrodinger to offer a trial version of Schrodinger2013 software to
carry out the in-silico studies. We also thank GUJCOST for providing financial support to carry out this
research project.
Combination of Pharmacophore, docking based virtual screening approaches to
identify potential CSF1R inhibitors.

Pa,an (umar %$S-
?
, Sarma +"#P
2
, #am8a8u @undla--
2
and (.#.S.Sam8asi,a#ao
?

?. *epartment o7 Biotechnology, "charya $agarLuna 0ni,ersity, $agarLunanagar @untur, ".P P.$3 P22 P?0.
2. @)(Biosciences P,t. <td. Plot $o. C&, .*", %allapur, /ydera8ad3P000CM
- Presenting "uthor! -- orresponding "uthor! Email: ram8a8u.gundla@g,k8io.com


SF3?# is a mem8er o7 the class ... receptor tyrosine kinases, along 9ith c3(it, Flt', and P*@F# [ and Q.
olony stimulatory 7actor ? 5SF3?6, also kno9n as macrophageDmonocyte colony stimulatory 7actor 5%3
SF6, 8inds to SF3?#, resulting in dimeri2ation, autophosphorylation, and acti,ation o7 signal transduction.
;o identi7y potent inhi8itors against SF?# 9e deployed rational approaches o7 drug disco,ery.
Pharmacophore models 9ere generated using a set o7 ?04 structurally di,erse compounds out o7 9hich ?&
9ere chosen as training set and OP as test set 9ith an inhi8itory acti,ity ranging 7rom 0.4 to ?000 n%
against s7?#. ;he model 9as ,alidated 8y test set 9ith a correlation o7 0.CP. )irtual screening 9as
per7ormed against "sinex data8ase. ;he ,irtual screening hits 9ere 7iltered 8y <ipinski rule. *ocking
analysis 9as per7ormed 7or a set o7 ,irtual hits 9ith high predicti,e acti,ity and structural di,ersity using
@lide. ;he predicti,e 8inding poses 9ere analy2ed and ?2 hits i.e the compounds 9ith producti,e
interactions in the acti,e site 9ere selected 7or pharmacological screening.


Pharmacophore-based virtual screening and density functional theory
approach to identify dual GPCRs inhibitors
,h. /hanachandra 'ingh and ;. ,arthikeyan2
/epartment of Aioinformatics" Alagappa 8ni!ersity" ,araikudi- 0.111*" $amil -adu" India
2CorrespondenceB mkbioinformaticsCgmail.com

Both GPCRs Endothelin (ET
A
) and Angiotensin II Receptor (AT
1
R) antagonists lower the blood
pressure in hypertensive patients. Thus, the combination of AT
1
R and ET
A
receptor antagonist may have
greater efficacy and broader utility compared with each drug alone. Ligand-based pharmacophore modeling
was used to identify the critical chemical features of AT
1
R and ET
A
receptor antagonist. The generated
pharmacophore model was validated using test set and decoy set methods. The best pharmacophore model
was used as a query in virtual screening to identify novel dual AT
1
R and ET
A
receptor antagonists.
Compounds selected by the best hypothesis in the virtual screening were tested for drug-like properties, and
molecular docking study was applied to determine the optimal orientation of the hit compounds in the AT
1
R
and ET
A
receptor canonical site. The 3D structures of the GPCRs were taken from our previous study. To
find the reactivity of the hit compounds, frontier orbital analysis was carried out using density functional
theory. AARRH was used as a 3D query in virtual screening of the Asinex and Chembridge databases. The
hit compounds were filtered using ADMET, Lipinski's Rule of Five, and successive molecular docking to
reduce the number of false positive results. Finally, 14 compounds were selected based on their critical
interactions with the active residues of AT
1
R and ET
A
receptor. To confirm the inhibitors' potencies, the
orbital energies, such as HOMO and LUMO, of the hit compounds and 5 training set compounds were
calculated. Among the 14 hit compounds, 7 compounds with the highest HOMO values were selected, and
this set was further culled to 3 compounds based on their energy gaps important for stability and energy
transfer. From the overall results, these 3 compounds were confirmed to be potential dual AT
1
R and ET
A
receptor antagonists that satisfied all the common pharmacophoric features.
Key words: Hypertension, DFT, HOMO, LUMO

Pharmacophore Based Virtual Screening for the Identification of
HDAC-6 Selective Inhibitors

Monika Sharma, Madhu Chopra*
Dr. B. R. Ambedkar Center for Biomedical Research,
University of Delhi, Delhi 110007, India
Email: monika.20april@gmail.com, mchopradu@gmail.com*


HDAC is one of the emerging targets in chemotherapy and is associated with many diseases/disorders such
as cancer, neurological and psychiatric. Current interest is of subtype specific HDAC inhibitors. Among the
Class- subtypes, HDAC 6 is an important therapeutic target. The emerging interest for HDAC6-selective
inhibitors is related to the modulation of acetylation of non-histone regulatory proteins implicated in cancer-
relevant processes, including cell migration, metastasis, angiogenesis and stress-response pathways. HDAC6
plays a role in aggresome formation and transport of ubiquitinated proteins for degradation through
proteasome degradation pathway. HDAC 6 prevent apoptosis due to misfolded proteins as it leads them to
degradation. The inhibitor of HDAC 6 reverses the effect by inducing it. To generate isoform selectivity,
modification of the cap group appears the most promising strategy. Typically efforts to design selective
inhibitors do not focus on manipulating the linker region. The HDAC enzymes show multiple grooves on
the surface of the protein around the binding site that are less conserved across the different isoform.The cap
groups are in a position to interact with these grooves. A second pocket close to the active site, believed to
be involved in product release, has been described as a tube-like pocket with a different shape in HDAC6
and HDAC8.Various HDAC 6 selective inhibitors have been developed using above strategy and points in
consideration.In the present study we used insilico approach to find HDAC6 selective inhibitors. To identify
new scaffolds specific for HDAC 6 inhibitors a quantitative pharmacophore hypothesis was developed for
virtual screening using Discovery Studio 2.5. Top ten resultant hypotheses were generated, among them
Hypo1 was selected as a best hypothesis based on the statistical parameters like high cost difference (81),
lowest RMSD (0.8331) and good correlation coefcient (0.943).The configuration cost is 15.7.
All the above statistical validations conrm that the chemical features in Hypo1(1 hydrogen bond acceptor,
1 hydrogen bond donor, and 2 hydrophobic features) constitute the pharmacophore for HDAC6 inhibitors.
Hence, Hypo1 was used as a query in virtual screening to nd the novel scaffolds by screening the available
chemical databases. The screened molecules from the databases were checked for the ADMET as well as the
drug-like properties. HDAC6 complex structure in PDB was used for molecular docking to nd out the
suitable orientation of hits in the active site.










Pharmacophore modeling and virtual screening for protein tyrosine phosphatase to
generate novel inhibitors against cancer

Lavanya Souda Padmarao, Aboubakr H. Abdelmonsef, Ramasree Dulapalli and Uma Vuruputuri*#;

Department of Chemistry, Nizam College, Osmania University, Basheerbagh,
Hyderabad 500001, Andhra Pradesh, India, # current address : University College of Science, Osmania
University, Hyderabad., Email: vuma@osmania.ac.in; vuma1957@gmail.com


Protein-tyrosine phosphatases (PTPs) play an important role in signal transduction
in eukaryotic cells, essential for cell proliferation, adhesion and migration. PTPs have a
significant role in both normal and pathological physiology. The regulation of PTP function
is associated with tumor genesis and progression in different types of human cancer (1).
The PTPs are potential druggable targets in design of new therapeutics against cancer.

In the present study, the 3D pharmacophore model of the PTP inhibitors is generated, using Phase module of
Schrodinger Suite. The database of active ligands with IC50 values ranging from 900 to 235600 (nM) were
studied. The pharmacophoric features were mapped onto the ligand structures and best pharmacophore
model (AADDR) described the key interactions. The pharmacophore model is considered and virtual
screening is carried out against the PTP to identify new leads for the design of effective potent PTP
inhibitors.

Keywords: Protein-tyrosine phosphatases, pharmacophore, virtual screening

References:
1. A stman, C Hellberg, FD Bhmer. Protein-tyrosine phosphatases and cancer, Nature
Reviews Cancer,6,2006, 307-320.

2. Yeong-Sheng Changa, Ling-Ling Yangb, and Bo-Cheng Wanga,
Pharmacophore Modeling of Tyrosine Kinase Inhibitors:4-Anilinoquinazoline,
Derivative. J.of the Chinese Chemical Society, 57, 2010, 916-924.

3. Fahad A Al-Obeidi1 and Kit S Lam. Development of inhibitors for protein tyrosine -kinases.
Oncogene,19, 2000, 5690-5701.

4. Kiran Kumar Mustyala, Annapurna Renee Chitturi, Prameela Subhashini Naikal James
and UmaVuruputuri.Pharmacophore mapping and in silico screening to identify new potent
leads for A2A adenosine receptor as antagonists.. Journal of receptors and Signal
Transduction, 32,2012,102-113.






Pharmacophore mapping and 3D QSAR Studies of A1 Adenosine Receptor
Kiran Kumar Mustyala, Vasavi Malkhed, Venkata Ramana Reddy Ch
#
and Uma Vuruputuri*
Department of Chemistry, University College of Science, Osmania University, Hyderabad, 500007, Andhra
Pradesh, India.
# Department of Chemistry, JNTUH CEH, JNT University, Kukatpally, Hyderabad, 500085, Andhra
Pradesh, India.*E-mail: vuma@osmania.ac.in, vuma1957@gmail.com

Adenosine Receptors (ARs) are members of the G-Protein-Coupled Receptors (GPCRs) family
1
.
ARs are classified into A1, A2A, A2B, and A3 subtypes. A1 subtype is expressed extensively in the central
nervous system (CNS) and in other tissues
2
. Antagonist binding to A1 plays a vital role in various
physiological functions. Identifying new A1 receptor antagonists goes a long way in discovery of selective,
non-toxic, therapeutic remedies
3
.
The 3D QSAR study of A1 Adenosine Receptor antagonists, is taken up to design the best
pharmacophore model based on 116 structurally diverse ligands to explore the requisite structural features
that affect the biological activity. The study was carried out on PHASE module of Schrodinger suite. Several
parameters like Hydrogen bond Acceptors (A), Donors (D), Aromatic rings (R) and Hydrophobicity (H) are
used to generate a Pharmacophore model which is validated using statistical analysis
4-5
. The model is
treated as a template to screen databases and novel antagonists for A1 AR are identified with potential
therapeutic value.
Figure: The best common pharmacophore
hypothesis is presented with best fit
molecule

Pharmacophore features are red vectors for
hydrogen bond acceptors (A), cyan vectors for
hydrogen bond donors (D), orange rings for aromatic
ring (R), green ball for hydrophobic function (H).



Key Words: 3D QSAR, Pharmacophore
mapping, Adenosine Receptors, Antagonist, PHASE
References
1. Kenneth A. Jacobson, Zhan-Guo G., Nature Reviews Drug Discovery. 2006, 5, 247.
2. Veli-Pekka Jaakola, Mark T. Griffith, Michael A. Hanson, Vadim Cherezov, Ellen Y.T. Chien, J. Robert
Lane, Adriaan P. Ijzerman, and Raymond C. Stevens, Science. 2008, 21, 322(5905), 12111217.
3. Campbell, R. M., Cartwright, C., Chen, W., Chen, Y., Duzic, E., Fu, J. M., Loveland, M., Manning, R.,
McKibben, B., Pleiman, C. M., Silverman, L., Trueheart, J., Webb, D. R., Wilkinson, V., Witter, D. J., Xie,
X., and Castelhano, A. L. Bioorg Med Chem Lett. 1999, 9, 2413-2418.
4. Dixon S. L.,Smondyrev A. M., Knoll E. H., Rao S. N., Shaw D. E., Friesner R. A., J. Comput. Aided Mol.
Des. 2006, 20, 647-671.
5. Dixon S. L., Smondyrev A. M., Rao S. N., Chem. Biol. Drug Des. 2006, 67, 370-372.







Prediction of mutagenic potential of nitroaromatics by atom based QSTR and Density Functional
Theory Calculations

Mihir P. Khambete
1
, Nilesh R. Tawari
2
, Harish S. Kundaikar
1
, Arundhati C. Lele
1
,
Mariam S. Degani
1*
1
Institute of Chemical Technology, Mumbai, Maharashtra, India
2
Strand Life Sciences, Bangalore, India, Corresponding author: *ms.degani@ictmumbai.edu.in

Nitroaromatic compounds are important industrial chemicals widely used in the synthesis of many diverse
products including drugs, dyes, polymers, pesticides and explosives. However the mutagenicity associated
with nitroaromatic compounds is a toxicological feature of great concern. On the other hand, there are
successful examples of non-mutagenic nitroaromatic molecules. In the light of this, to predict the
mutagenicity of nitroaromatic compounds, an atom based QSTR model was generated. A wide variety of 5
and 6 membered monocyclic and fused ring systems were selected as dataset for the studies. Additionally
molecules were studied by complete geometry optimization using DFT at B3LYP/3-21G* level of theory.
The visualization of different properties highlighted key inferences. These include the likelihood of
mutagenicity for the molecules with more fused planar hydrophobic rings having hydrogen bond acceptor
and electron donating substitutions. Also all highly mutagenic compounds have two or more negative
potential regions. Specific electronic properties such as HOMO and LUMO indicate that most of the
mutagenic molecules are very reactive in nature. The results of this study would be useful as a predictive
tool to screen mutagenic nitroaromatics and design safer non-mutagenic nitro compounds.













Investigation on selectivity of novel Beta-Amyloid Precursor Protein (-APP) inhibitors
using chemical feature based pharmacophore modeling, molecular docking and density
functional theory approaches.


C. Loganathan, S. Kabilan*
Department of chemistry, Annamalai University, Annamalai nagar, Chidambaram 608 002.
kabilan@gmail.com


The Beta-amyloid precursor protein (-APP) is a membrane-bound glycoprotein which has been proposed to
play a role both as a growth factor and a mediator of cell adhesion. The source of the fibrillogenic amyloid
beta-peptide that accumulates in the brain of victims of Alzheimer's disease is a multifunctional protein that
is widely expressed in the nervous system. Chemical feature based pharmacophore model, molecular
docking and density functional was developed for selective -APP inhibitors, which provides an efficient
way to discuss the isoform selectivity of -APP inhibitors. Pharmacophore model was generated. The best
hypothesis (Hypo1) consisting of four chemical features (one hydrogen bond donor , one hydrophobic and
two ring aromatic) has exhibited high correlation co-efficient of 0.9694, cost difference of 64.96 bit and low
RMS value of 0.8030. It was further validated by test set and decoy set to prove its robustness and statistical
significance. The well validated model was used as 3D query in the virtual screening to retrieve potential
leads for -APP inhibition. The hit molecules were further sorted out by applying drug like filters such as
Lipinskis rule of five and ADMET (absorption, distribution, metabolism, excretion, and toxicity)
properties. Molecular docking was performed to find suitable orientation of compounds in the protein active
site. The lead compound was subjected to DFT approaches, frontier orbitals HOMO and LUMO values
clearly indicates an important role of charge-transfer interactions with the binding site in the receptor for
potent activity. The results contribute to our understanding of the molecular mechanism underlying the
selectivity of -APP inhibitors and suggest a possible target region to design novel selective -APP
inhibitors.

Key words: Beta-amyloid precursor protein, Pharmacophore modeling, Molecular docking and density
functional theory.




Study of 3D QSAR properties of Semicarbazone as Anticonvulsant

Surya Prakash
1
*, Partha Chowdhury
1
, Jainendra Jain
1
, Reema Sinha
1
Department of Pharmacy, Ram-Eesh Institute of Vocational and Technical Education, 3, Knowledge
Park-1, Greater Noida, G.B. Nagar, U.P-201310, India


Gama amino butyric acid (GABA) is a major inhibitory neurotransmitter responsible for action of most of the
anticonvulsant compounds. Gama amino butyrate amino transferase (GABAAT) is one of the most important targets in
the design and discovery of successful anticonvulsants.
The present study is based on 3D QSAR studies of 20 Semicarbazone derivatives (S
1
-S
20
). QSAR models were further
validated for statistical significance and predictive ability by internal and external validation. All 20 molecules were
subjected to 3D QSAR studies using Random Selection and Sphere Exclusion Method with Multiple Regression (MR)
and Partial List Square Method (PLS) to study the features responsible for anticonvulsant activity of semicarbazones. The
model displayed r
2
and q
2
value of r
2
=0.9516, q
2
= 0.8916 respectively for 16 compounds in training set and 4
compounds in test set.
The hydrogen bond accepter, hydrogen bond donor, positively charged ion, aromatic carbon, steric and hydrophobic
parameters are the important features, contributing towards the activity. The model was found to be highly predictive.
The steric descriptor (S_116) indicates that the phenyl ring must be substituted with an electronegative group at para
position. Thus it would be worthwhile to synthesize various semicarbazone derivatives having more numbers of
electronegative substitutents on phenyl ring.


Pharmacophore Mapping, 3D QSAR and Docking Studies on inhibitors of Prolyl oligopeptidase
(POP)



Mohan Babu Jatavath, Sree Kanth Sivan and Vijjulatha Manga*

%olecular %odeling and %edicinal hemistry @roup, *epartment o7 hemistry,
$i2am ollege, >smania 0ni,ersity, Basheer8agh, /ydera8ad G P00 00?,
Layam??CO4@gmail.com ,vijjulathamanga@gmail.com$




Prolyl oligopeptidase(POP) is a serine endopeptidase that hydrolyses proline containing peptides shorter than 30
amino acids. POP may be associated with cognitive functions, possibly via the cleavage of neuropeptides. Recent
studies have also suggested novel non-hydrolytic and non-catalytic functions for POP, it has also been proposed as a
regulator of inositol 1,4,5-triphosphate signaling and several other functions such as cell proliferation and
differentiation, as well as signal transduction in the central nervous system, and it is suspected to be involved in
pathological conditions such as Parkinsons and Alzheimers diseases and cancer.

POP inhibitors have been developed to restore the depleted neuropeptide levels encountered in aging or in
neurodegenerative disorders. We report 3D-QSAR analyses based on Pharmacophore modeling on Prolyl
oligopeptidase(POP) in order to have a better understanding of the structure-activity relationship of these compounds.
Five point Pharmacophore with two hydrogen bond acceptor (A), one hydrophobic group (H) and two aromatic rings
(R) as pharmacophoric features was developed. Amongst them the pharmacophore hypothesis AAHRR41 yielded
statistically significant 3D-QSAR model with 0.9135 as R
2
value and 0.6522 as Q
2
value, was considered to be the
best pharmacophore hypothesis. The developed Pharmacophore model was validated by predicting the activity of test
set molecules. The squared predictive correlation coefficient of 0.8278 was observed between experimental and
predicted activity values of test set molecules. These inhibitors were docked into the protein using Glide 5.6 to
understand the binding mode. The results obtained from 3D QSAR and docking study was used for rational design of
potent inhibitors against Prolyl oligopeptidase(POP).

Computational strategy to design novel C5-curcuminoids against cancer

K. Kranthi Raj
a
, Anuj Thakur
a
, Sanjay V. Malhotra
b
and Diwan S. Rawat
a
*
a
Department of Chemistry, University of Delhi, Delhi-110007, India
b
Laboratory of Synthetic Chemistry, SAIC-Frederick Inc., National Cancer Institute at Frederick, 1050 Boyles Street, Frederick,
MD 21702, USA, *Corresponding author. e-mail: dsrawat@chemistry.du.ac.in

Curcumin, a dietary pigment isolated from the rhizome of curcumin longa linnaeus has been well known as chemopreventive
agent since ages. Due to its wide biological applications plethora of work has been done on this pharmacophore [1-5] and resulted
many potent molecules, and mono carbonyl analogues [6-11] were one such class of compounds. As a part of our on-going
programme towards the development of medicinally important molecules [12-22] we became interested in the design and
development of novel anti-cancer compounds based on mono carbonyl analogue of curcumin. In the present work mono carbonyl
analogues of curcumin (MNC) were considered for further enhancing its colorectal anti-cancer activity against using both
structure based and ligand based drug discovery. Quantum mechanical polarised ligand docking (QM-PLD) has given reliable
and effective results when compared with rigid receptor and induced fit docking. As a part of ligand based drug discovery, atom
based three dimensional quantitative structure activity relationship (3D-QSAR) model with pharmacophore alignment was
constructed comparing with flexible ligand alignment based model. Generated pharmacophore based QSAR model has shown
predominant correlation coefficient r
2
(0.91) and test set prediction coefficient q
2
(0.82). The correlated results of QM-PLD and
pharmacophore based 3D-QSAR had provided comprehensive information regarding the binding orientation and suggested
structural changes for anti-cancer activity enhancement. Based on information acquired from the above studies different MNCs
were synthesized and tested for its anti-cancer activity. These synthesized compounds, tested in vitro were in significant
agreement with in-silico predictions observed. Compounds ATH-57 and ATH-78 has shown promising anti-cancer activity than
the reported MNCs [23]. These lead compounds have desirable physicochemical properties and are excellent candidates for
further optimization.
References
1. Hussain, A. R.; Al-Rasheed, M.; Manogaran, P. S.; Al-Hussein, K. A.; Platanias, L. C.; Al Kuraya, K.; Uddin, S.
Apoptosis 2006, 11, 245.
2. Beevers, C. S.; Li, F.; Liu, L.; Huang, S. Int. J. Cancer 2006, 119, 757.
3. Johnson, S. M.; Gulhati, P.; Arrieta, I.; Wang, X.; Uchida, T.; Gao, T.; Evers, B. M. Anticancer Res. 2009, 29,
3185.
4. Shankar, S.; Chen, Q.; Sarva, K.; Siddiqui, I.; Srivastava, R. K. J. Mol. Signal. 2007, 2, 10.
5. Prasad, C. P.; Rath, G.; Mathur, S.; Bhatnagar, D.; Ralhan, R. Chem. Biol. Interact. 2009, 181, 263.
6. Yadav, B.; Taurin, S.; Rosengren, R. J.; Schumacher, M.; Diederich, M.; Somers-Edgar, T. J.; Larsen, L. Bioorg.
Med. Chem. 2010, 18, 6701
7. Das, U.; Sharma, R. K.; Dimmock, J. R. Curr. Med. Chem. 2001, 2009, 16
8. Lagisetty, P.; Powell, D. R.; Awasthi, V. J. Mol. Struct. 2009, 936, 23
9. Katsori, A. M.; Chatzopoulou, M.; Dimas, K.; Kontogiorgis, C.; Patsilinakos, A.; Trangas, T.; Hadjipavlou-
Litina, D. Eur. J. Med. Chem. 2011, 46, 2722
10. Lagisetty, P.; Vilekar, P.; Sahoo, K.; Anant, S.; Awasthi, V. Bioorg. Med. Chem. 2010, 18, 6109
11. Makarov, M. V.; Leonova, E. S.; Rybalkina, E. Y.; Tongwa, P.; Khrustalev, V. N.; Timofeeva, T. V.; Odinets, I. L.
Eur. J. Med. Chem. 2010, 45, 992.
12. Aggarwal, N.; Kumar, R.; Dureja, P.; Rawat, D. S. J. Agric. Food Chem. 2009, 57, 8520
13. Manohar, S.; Khan, S. I.; Rawat, D. S. Bioorg. Med. Chem. Lett. 2010, 20, 322










Computational Approach using Open Source Software: HDAC Inhibitors for Alzheimer's disease.

P. Ajith kumar, A. Bhargavi, Y. Kavitha, A. Rajasekhar reddy,
*
K. Umasankar, B. Shireesha

Medicinal Chemistry Research Division, Vaagdevi College of Pharmacy, Warangal-506001, India, *Corresponding
E. mail: youmasankar@gmail.com




HDAC enzymes are new targets for the treatment of AD disease, and development of more potent and
selective HDAC inhibitors is an important biological objective. For the better HDAC inhibition,
inhibitors should have cap, linker with six carbon chain length and zinc binding group. To get good
candidate, we used some open source software. Based on the pharmacophore model, nearly 230
molecules of HDAC inhibitors designed with phenyl hydrazone as cap, thiazole ring as linker and
hydroxamic acid as zinc binding group. The molecules were constructed and designed as library by
using MarvinSketch software. Pharmacokinetics (ADME) of all the 230 compounds in the human
body were analyzed by using Lipinskis Rule of five. The passed compounds were subjected to toxicity
prediction by using OSIRIS Property Explorer. The pharmacological activity and their possible target
of action were predicted by PASS Online for good candidates. The compounds having
Neuroprotective, Anti Alzheimers, Lipid peroxidase inhibitory activity were selected and top hits
were selected for synthesis and was evaluated by using various in vivo and in vitro screening methods.
Some of the molecules exhibited promising activity.

















Toxicity Studies (OSIRIS Property Explorer)
Lipinski Rule of Five
Activity Prediction PASS
Identification of HITs
Figure 1: Steps in virtual screening for design of molecules
PREDICTING METABOLIC STABILITY AND TOXICITY OF SOME SMOOTH
MUSCLE RELAXANTS

R. P. Dhavale*, A. R.



Suryavanshi, M. S. Bhatia, H. N. More
Bharati Vidyapeeth College of Pharmacy, Kolhapur



The site of biotransformation, the extent and rate of metabolism and the number of active metabolic
pathways are among the most important characteristics of the pharmacokinetics of a drug. The
cytochrome P450 (CYP P450) enzymes are the major catalysts involved in the metabolism of drugs.
Bioavailability and toxicity are the most common barriers in drug development today, and P450 and
the conjugation enzymes can influence these effects. Different isoforms of Cytochrome P450
metabolize different types of substrates (or drugs) and make them soluble during biotransformation.
Therefore, fate of any drug molecule depends on how they are treated or metabolized by CYP
isoforms. There is a need to develop models for predicting substrate specificity of major isoforms of
P450, in order to understand whether a given drug will be metabolized or not. In this project, In-
silico methods for predicting the metabolizing capability of major isoforms (e.g. CYP 3A4, 2D6,
1A2, 2C9 and 2C19) for drug molecules would be used to achieve metabolic and toxicity analysis of
in-house leads. The present work describes the interactions of in-house leads of various classes of
smooth muscle relaxants with predetermined set of metabolic enzymes. The metabolic study and
toxicity profile of the in-house leads were predicted using various CYP 450 isoforms with
Molecular Design Suite (V-life) and Glide (Schrodinger) suite.

Keywords: CYP 450, Bioavailability, isoforms, pharmacokinetics



The Prediction of Site of Metabolism (SOM) in ligands, metabolized by CYP3A4 Enzyme:
Comparison of Glide XP and Induced Fit Docking (IFD)

Deepak K. Lokwani
a
, Aniket P. Sarkate
a
, Nanasaheb B. Dharbale
b
, Devanand B. Shinde
a
*

a
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad-431004 (MS),
India,
b
Shree Bhagwan College of Pharmacy, Aurangabad, 431003 (MS), India dklokwani@gmail.com,
dbsdeepak10@rediffmail.com


CYP3A4 is most important enzyme from Cytochrome P450 superfamily, metabolizing approximately half
of the currently marketed drugs, besides endogenous compounds. To metabolize such a variety of
compounds, CYP3A4 has to be an extremely flexible structure. The available native (ligand unbound) and
ligand bound crystal structures of CYP3A4 in Protein Data Bank (PDB) have showed the high flexibility of
amino acid residues in side chain and loop region, thus making binding pocket in a closed and open
conformation respectively. The RMSD values of superimposition of C-alpha carbon atoms of available
crystal structures were measured, which ranges from 1.66 to 10.54 . This confirmed that every ligand
induces different conformational changes into binding pocket of CYP3A4 enzyme and thus make ligand-
enzyme interaction studies difficult. We employed Glide XP and Induced Fit docking (IFD) to study their
ability to reproduce and analyze the binding mode of ligands (Ketoconazole, Metyrapone and Ritonavir
extracted from PDB crystal structures) and to predict their site of metabolism (SOM) into the native and
ligand bound crystal structures of CYP3A4. The best ligand-enzyme complex was selected for each ligand
as per desired metabolic pose of drug candidate, and further analyzed by measuring distance of ligand atom
from heme Fe and by superimposing on corresponding PDB crystal structure. The complete study was
further applied to seven more ligands whose ligand-enzyme complex crystal structure is not available in
PDB. As the flexibility issue concerned with CYP3A4, Glide XP docking is unable to predict the desired
metabolic pose of some of ligands and IFD produces at least one desired ligand-enzyme complex for number
of ligands for all crystal structures. IFD therefore was found to be one of the reliable methods for predicting
and analyzing the site of metabolism of ligands in the flexible binding pocket of CYP3A4.







Adventures in Chemical Space: Utility of Constitutional Isomers in Drug Discovery
Sona Warrier and Prashant S. Kharkar
SPP School of Pharmacy and Technology Management, SVKMs NMIMS, V. L. Mehta Road, Vile Parle (W), Mumbai
India.
We have lately been interested in exploring a new perspective on constitutional isomers as a means of venturing
into novel chemical space. We stumbled upon this idea accidentally. The basic idea is to enumerate possible
constitutional isomers for a give n molecular formula of a lead/drug.
isomers can be used for any and every structure

Venturing into novel chemical space ba
Model. 2013 (Manuscript under preparation).













Adventures in Chemical Space: Utility of Constitutional Isomers in Drug Discovery
Sona Warrier and Prashant S. Kharkar
*
PP School of Pharmacy and Technology Management, SVKMs NMIMS, V. L. Mehta Road, Vile Parle (W), Mumbai
India.
prashant.kharkar@nmims.edu
We have lately been interested in exploring a new perspective on constitutional isomers as a means of venturing
into novel chemical space. We stumbled upon this idea accidentally. The basic idea is to enumerate possible
ve n molecular formula of a lead/drug.
1
Once enumerated, the database of constitutional
isomers can be used for any and every structure- and/or ligand-based approaches such as 3D pharmacophore search,
molecular docking, shape
based similarity search, etc. Figure 1 depicts an
example of the strategy. This concept can
also be applied to substructure search in a
lead/drug molecule. An expert medicinal
chemist's intuition is the key to the
successful outcome of this strategy. In our
opinion, this is the first conscious attempt to
address the usefulness of constitutional
isomers in lead discovery and development.
Figure 1. Few select constitutional
isomers of Omeprazole
Reference
1. Kharkar, Prashant S.
Venturing into novel chemical space bases on constitutional isomer-based search.
(Manuscript under preparation).
Adventures in Chemical Space: Utility of Constitutional Isomers in Drug Discovery
PP School of Pharmacy and Technology Management, SVKMs NMIMS, V. L. Mehta Road, Vile Parle (W), Mumbai-400016.
E-mail:
We have lately been interested in exploring a new perspective on constitutional isomers as a means of venturing
into novel chemical space. We stumbled upon this idea accidentally. The basic idea is to enumerate possible
Once enumerated, the database of constitutional
based approaches such as 3D pharmacophore search,
molecular docking, shape- and electrostatics-
larity search, etc. Figure 1 depicts an
example of the strategy. This concept can
also be applied to substructure search in a
lead/drug molecule. An expert medicinal
chemist's intuition is the key to the
successful outcome of this strategy. In our
this is the first conscious attempt to
address the usefulness of constitutional
isomers in lead discovery and development.
Few select constitutional
isomers of Omeprazole
Kharkar, Prashant S.
based search. J. Chem. Inf.
Identification of potential targets for screening and development of radiation
countermeasure agents using chemoinformatic approaches

Jayadev Joshi & I. Prem Kumar

Radiation Biosciences
Institute of Nuclear Medicine and Allied Sciences
Defence Research and Development Organization
Brig SK Majumdar Road, Timarpur, Delhi
jaidev53ster@gmail.com

Free radical mediated damage to cellular macromolecules and subsequent cell death and organ dysfunction
has been well attributed to radiation mediated acute and long term effects. Owing to multi-factorial
involvement development of potential drugs for protection against radiation mediated damage has been
appreciated to be a formidable challenge and till now there are no clinically approved drugs for radiation
over exposures. Screening and re-purposing of pharmacopoeia is an approach of high translatability.
However screening of large number of small molecules in vertebrate models is still a major hurdle.
Chemoinformtics mediated prioritization of large number libraries is an effective alternative for
identification of radioprotectors. Systematic data mining, careful analysis and identification of potential
targets hold key for the successful screening. In this study systematic screening of already reported
(available on public databases) radioprotectors was performed and was found that around 29% of reported
molecules (40 out of 138) have a role in inflammatory pathways. Baclomethasone dipropionate, a known
potential radioprotector (in phase I clinical trials) with reported anti-inflammatory action was used as lead
compound for further structure and function based similarity and screening purposes. Data mining lead to
identification of glucocorticoids as potential functional target for baclamathasone dipropionate. Screening of
Johns Hopkins Clinical compound Library, a collection of around 1400 FDA approved small molecules,
against glucocorticoid receptor has lead to identification of a number of previously unknown molecules.
Further these molecules were further prioritized based on the similarity ranking and analysis, evaluated for
possible radiation protection using developing zebrafish as a vertebrate model. Among them a compound
(code named as 7G) has been found to be effective in rendering protection to zebrafish embryos from lethal
and damaging effects of ionizing radiation with a survival advantage of 60%. The detailed study,
methodologies employed and results will be discussed in detail during presentation.










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(.E; School o7 Pharmacy, ?' (m. Stone, @ha2ia8ad %eerut #oad, @ha2ia8adG20?20M, .ndia
-"uthor 7or correspondence A Presentation! E3mail: t%s.?#$+C,mai(.com! %o8ile: 0&CPM'PO?0C
1?'9,159
;he main o8Lecti,e o7 our rational drug design is to predict the 8est no,el short chain peptide leads 7or analgesic
e77ect 7rom the designed set o7 templates 9ith ,arious descriptors such as Boman index, <ipinski rules and molecular
dynamics simulations. Ie 8uilt sixty 7i,e candidate molecules 520 tripeptides! 4P tetrapeptides6 7rom chemical
templates and su8Lected to Boman index analysis through online antimicro8ial peptide data8ase. ;he 8est resulting
eighteen templates 5' tripeptides! ?P tetrapeptides6 deri,ed 7rom this data8ase 9ere passed through empirical
lipinski 7ilters to assess drug like properties using ,arious molecular descriptors namely %olecular mass, Partition
coe77icient, /ydrogen 8ond donors and /ydrogen 8ond acceptors respecti,ely. <ater, 9e conducted molecular
dynamics on the 8est resulting templates 9ith t9enty nanosecond simulations o7 total atoms at an a,erage
temperature 2&O.?P( in hundred steps 9ith applying constraints to all 8onds in pure 9ater. Finally, the
con7ormational sta8ility o7 the candidates 9ere analy2ed 9ith measurement o7 ;otal potential energy, ;otal (inetic
energy, Bond stretch energy, Bond angle 8ending energy, ;orsion angle energy, #estraining torsional energy and
/ydrogen 8ond energy. .n addition, the proteinGligand 8inding 9as tested 9ith <ennard Lones energy and
Electrostatic energy 7or all the 8est templates. "mong the results o8tained 9ith molecular dynamics 7or ,arious nonG
8onded interactions, 9e identi7ied Phe3<ys3@ln3;yr 5F(1T6, Phe3;rp3<ys3;yr 5FI(T6, Phe3/is3"rg3;yr 5F/#T6 and %et3
%et3Phe3;yr 5%%FT6 as potent tetrapeptide leads 9ith maximum con7ormational sta8ility 7or analgesic e77ect
among the selected sixty 7i,e template sets.
Key words
;etrapeptides! Boman index! <ipinski rules! %olecular dynamics! "nalgesics! #ational drug design















Protein Modeling and
Bioinformatics











*E'I;/I/; 1 5+MM+/ &155I/E 51/*I*19E -'I/; ,E&E,'E &155I/+=+;H @+, M-=9I2=E 219!+;E/'
51-'I/; ?159E,I1= E/*+51,*I9I'
*r3M3 Menak(a and *r3'3&i7ayakumar
*epartment of ?otany and Micro)iology
13&3&3M3 'ri 2us(pam 5ollege (1utonomous"8 2oondi8 9(an7avur M *t3
1)stract
Endocarditis, a heart disease, is an in7lammation o7 the inner layer o7 the heart. Bacterial endocarditis is a
li7e3threatening in7ectious disease caused 8y streptococcal and enterococcal 8acteria, 9hich produce pathogenic
en2ymes such as SsaB 7rom Streptococcus san,uinis, Sca" 7rom Streptococcus ,or%onii, Psa" 7rom Streptococcus
pneumoniae, Fim" 7rom Streptococcus parasan,uis, Sc8" 7rom Streptococcus cristatus and E7a" 7rom 5nterococcus
faeca(is, 8elonging to the <ra. 7amily. urrently, treatment o7 8acterial endocarditis 9ith anti8iotics is really a maLor
challenge 8ecause o7 the resistance de,eloped 8y the 8acteria against anti8iotics. /ence, ,accines 9ill e,entually 8e
the predominant alternati,e approach 7or treatment and pre,ention o7 endocarditis. ;he con,entional approach to
,accine de,elopment re:uires more time 7or the culti,ation and processing o7 pathogens to identi7y the components
o7 immune system. ;o day, proteomics in7ormation helps in studying ,accine de,elopment through in si(ico 9ithout
the need o7 culti,ating the pathogen. ;his approach, called \re,erse ,accinology], reduces the time re:uired 7or the
identi7ication o7 candidate ,accines and pro,ides ne9 solutions 7or peptide ,accine de,elopment. /ence, the
present study has 8een under taken to identi7y the peptide ,accine candidate 7or multiple pathogens causing
di77erent kinds o7 endocarditis through re,erse ,accinology. From the study, the 7ollo9ing 7indings 9ere made.
" strong 8inding a77inity o7 .g% 9ith all the <ra. 7amily o7 en2ymes 9as o8ser,ed, 9hich re,ealed that .g%
9as the most e77ecti,e anti8ody that could 8e used against 8acterial endocarditis. ;he antigenicity and topology
studies sho9ed that all the en2ymes o7 <ra. 7amily 9ere :uali7ied to act as antigens. From the antigens, B3cell and ;3
cell epitopes 9ere predicted using ,arious 8ioin7ormatics tools. Finally, single ;3cell epitope 9as selected 7rom the
predicted ;3cell epitopes, as :uali7ied ,accine candidate and get con7irmed as su8unit ,accine candidate suita8le 7or
anti8ody production 8y the Peptide station at S9eden. ;he :uali7ied su8unit ,accine candidate 9as also tested
against ,arious pathogens causing di77erent endocarditis and the results con7irmed the suita8ility o7 the ,accine
candidate as a common su8unit ,accine candidate 7or multiple pathogens causing endocarditis.













Cross talk of AchE inhibitors with Nicotinic Acetylcholine Receptors
Leela Madhuri Chalasani, Nayak P
1
, Venkateswara Rao Talluri, Jayakumar Singh Bondili*
Centre for Bioinformatics, Department of Biotechnology, K L University,
Vaddeswaram, Guntur District -522502, AP - India.
1
Department of Physiology, NRI Medical College, Guntur Dist. AP- India.
Nicotinic Acetylcholine Receptors (nACHRs) are ligand gated ion channels, which play a key role in
neuronal transmission in central and peripheral nervous systems. These receptors are activated primarily by
agonists like acetylcholine, nicotine etc. These nACHRs are well-recognized as multi-drug targets and any
perturbation in the binding of the ligands results in addiction and other neurodegenerative diseases like
Schizophrenia, Parkinsons and Alzheimers disease (AD). Specifically, early stages of AD are identified
with deficiency in Acetylcholine levels and till date, only four drugs Donepezil, Galanthamine, Rivastigmine
and Tacrine have been approved by the FDA for the symptomatic relief of AD. These drugs block
Acetylcholine Esterase (AchE) present in the synaptic cleft effectively, increasing the concentration of the
acetylcholine and thereby enhancing cognition. However, the binding affinities of these inhibitors to
nACHRs and the biology of sensitized/ desensitized effects of these interactions are not fully understood.
In this study, the possible effects of the FDA approved AchE inhibitors on alpha 7- nACHRs were
investigated using comparative modeling, molecular docking and simulations. The Ligand Binding Domain
(LBD) of alpha 7 nACHR was modeled in both open and closed states. Molecular docking studies were
performed with four FDA drugs and compared alongside agonists- acetylcholine, choline, nicotine in open
(O), closed (C) and closed induced fit states (IF). The XP dock scores for the AchE inhibitors with alpha-7
nACHr were Donepzil -9.31(O) -11.72 (C) -14.96 (IF); Galanthamine -9.68 (O) -3.76 (C) -16.34 (IF);
Rivastigmine -9.55 (O) -9.82 (C) -13.27 (IF); Tacrine -5.82 (O) -1.02 (C) -13.30 (IF). Molecular dynamic
simulations for 10ns were carried out for best scoring induced fit docked complexes to investigate the
stability in the binding pocket. Overall this study provides an insight into the molecular interactions of AchE
inhibitors with nACHRs; giving us a chance to draw a plausible hypothesis of cross talk leading to the
sensitization / desensitization of the receptor.








Comparative Pathway Analysis, Homology Modeling, Virtual screening and ADMET
testing to find potential inhibitors against Aeromonas hydrophila and Pseudomonas
aeruginosa
Swapna Kale, Pooja Gaikwad, Manoj Damale*, Archana Panche, Chaitanya Chakre AND
Sanjay Harke
MGMs Institute of Bio-Sciences and Technology, Aurangabad, Maharashtra, India-431003

The identification and optimization of potential lead molecules are essential in order to establish multi drug
therapy against pathogenic organisms. Aeromonas hydrophila and P. aeruginosa are capable of causing
disease in humans who may acquire infections through open wounds or by ingestion of an adequate number
of the organisms in water or food. These bacteria can digest materials such as gelatin, hemoglobin, and
elastin and also interfere with the human immune system's defense mechanisms. The degradative enzymes
from these bacteria permanently disrupt the cell membranes and connective tissues in various organs. The
metabolic pathways are series of
chemical
reactions occurring within a
cell
. They are important in maintenance
of
homeostasis
within an
organism
. The comparative metabolic pathway analysis is done using metabolic pathway
database Metacyc to find out potential enzymes that will acts as drug targets. The potential drug targets
whose experimental structures are not available, structures of those are constructed using homology
modeling by primeX. The modeled structures are evaluated and used for further study like virtual screening
using Combi-Glide to find potential hits in NCI database. The potential hits are subjected for invitro
ADMET testing to check their drug like property using QikProp. The study will help in identification of new
inhibitors to treat conditions such as GIT disorder, Respiratory disorder, Urinary tract infection, cellulitis,
myonecrosis, and eczema.
Keyword: Drug Target, Aeromonas hydrophila, Pseudomonas aeruginosa, Metacyc, Homology modeling,
Virtual screening and ADMET testing.
Corresponding Author: Manoj Damale, mail2manoj @mgmibt.com










Activation-induced cytidine deaminase: A promising target for
drug designing and therapy

Mahesh Hegde
1, 2
, K. S. Rangappa
2
and Sathees C. Raghavan
1

1 Department of Biochemistry, Indian Institute of Science, Bangalore-12, India
2 Department of Studies in Chemistry, University of Mysore, Mysore-06, India

Activation-induced cytidine deaminase (AID) is a DNA editing enzyme that plays a major role in
somatic hypermutaion, class switch recombination and Ig gene conversion there by instigating antibody
diversification. AID is a member of the cytidine deaminase family and closely related to apolipoprotein B
RNA-editing cytidine deaminase 1, which converts cytosine to uracil in RNA. In certain cases, due to its
mutagenic role as well as hyperactivity, AID confers carcinogenicity in human, for example follicular
lymphoma (FL), oral squamous cell carcinomas, colon cancer etc. AID as a target has not been explored in
cancer therapeutics so far. Here, for the first time, we have identified novel inhibitors for the AID enzyme
using homology modeling, virtual screening and molecular dynamic simulation analysis. Despite having
maximum identity in APOBEC family proteins, the bioinformatics results suggested that these inhibitors are
more specific to AID. This study could help in finding new paradigms for the cancer therapy where AID
protein is responsible for oncogenesis.



















Insilico Modeling And Docking Studies On Cytotoxin Associated Gene A
(Caga ) in Helicobacter Pylori
Aditee Dalvi & Nirupama Narayan
Department of Bioinformatics, G. N. Khalsa College, Matunga, Mumbai India.

Contact: aditeedalvi10@gmail.com, cnnarayan14@gmail.com
Helicobacter pylori is a gram-negative bacterium which causes chronic gastritis and plays important roles in
peptic ulcer disease, gastric carcinoma. H. pylori have been found in the stomachs of humans in all parts of
the world. In Helicobacter pylori CagA protein is considered to be one of the virulence factors associated
with gastric cancer. The organism which express the product of the cytotoxin associated gene A(CagA) are
associated with duodenal ulceration Future studies in these areas will be critical to uncover molecular
mechanisms of chronic inflammation-mediated oncogenic transformation and provide options for cancer
prevention and intervention. The aim of this study was to estimate the magnitude of the risk for gastric
cancer associated with cagA seropositivity and to identify any sources of heterogeneity between studies. The
3D structure of cagA protein was modeled using homology modeling. The evaluation of the constructed
model is done by Structural Analysis and Verification Server (SAVS). Dr Duke's Phytochemical and
Ethnobotanical, ChemSpider and Drug Bank databases is used to find ligands. These compounds were
docked with the modeled structure, and those showing least Binding Energy (E value) were selected. These
results will be correlated by further statistical analysis.
Keywords: Helicobacter pylori, cagA, peptic ulcers, homology modeling, protein characterization, docking.
















Molecular modelling of the V.cholera LuxO and a virtual screening studies for the identification of novel
inhibitors
Hema.M, Karthi Shanmugam, and Adline Princy S
*

Quorum Sensing Laboratory, SASTRAs Hub for Research and Innovation (SHRI), SASTRA University, Thanjavur 613
402, Tamil Nadu
Abstract
Bacteria use a cell-to-cell communication activity termed "quorum sensing" to coordinate to perform
collective activities in a cell density dependent manner. Vibrio cholerae, a pathogen that causes an acute
disease, uses three parallel QS to interestingly show opposing behavioural activities of virulence factor
production at low cell density (LCD) and biofilm formation at high cell density (HCD). In this context, we
have identified LuxO, the central NtrC-type response regulator as our molecular target as it controls the
global (three parallel) V. cholerae QS cascade. In the present study, we used computational methods to
model LuxO and simulated the interactions of LuxO. Since no structural details of the proteins were
available, we employed homology modelling to construct the three dimensional structures. The modelled
proteins were validated and subjected for high throughput virtual screening. This allowed us to predict the
binding modes of the proteins to elucidate probable sites of interference.

















2rotein 'equence 1ctivity ,elations(ips (2ro'1,"
Naseemussalam
1
, MadhaviSastry
2
and Sachchidanand
3

National Institute of Pharmaceutical Research-Hajipur, Patna, Bihar, India

%odi7ied protein or en2yme can 8e designed 9ith ne9 or desira8le 7unction using protein engineering
techni:ue. Since it is a time consuming and expensi,e process, it is 8etter to go 7or some amino acid
su8stitution 5""S6 prediction tools 7irst rather than directly going to protein engineering. ProS"# 5Protein
Se:uence "cti,ity #elationship6 is one o7 the ""S prediction tool. .t can predict the acti,ity o7 a protein
,ariant in the presence o7 the training dataset 5protein se:uences and corresponding acti,ities6. .nitially it
9ill align the training set se:uences, and then it 9ill code the mutated residues that are present in the
training set. >nce that o,er, ProS"# 9ill 7ind out the contri8ution o7 each residue to the acti,ity o7 the
protein 8y calculating regression coe77icients using linear model. So i7 the user gi,es the test set se:uences,
ProS"# 9ill directly calculate its acti,ities. .7 user don=t ha,e the test set, ProS"# 9ill automatically
generate all possi8le com8inations o7 test set se:uences and predict their acti,ities.
ProSAR can be validated by comparing the predictions from different AAS prediction tools like I-
Mutant, PoPMuSiC, Mupro, SDM etc and through the structural analysis by Maestro and BioLuminate. For
the structural analysis using Maestro, first prepare the protein and its mutants through prime Homology
modeling and compare these structures. In case of BioLuminate, prepare the protein and its mutants using
Loop and Residue mutation panel and compare these structures.
1
First author, E-mail: nasjas2006@gmail.com
2
Main guide, Senior Application Scientist, D E Shaw & Co, E-mail: Madhavi.Sastry@deshaw.com
3
Co-guide, Associate Professor,NIPER,Hajipur, E-mail: sachchi@gmail.com











Structural comparison of P-glycoprotein and MRP for substrate specificity
Pankaj Kumar, Rameshwar Prajapati, Rohit Bansal, Abhay T. Sangamwar*
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research
Sector 67, S.A.S. Nagar, Punjab-160062
Abstract
P-glycoprotein (Pgp) and multidrug resistance protein (MRP) are two most widely expressed members of ATP-
binding cassette (ABC) efflux transporters. Over-expression of these transporters is associated with multidrug
resistance to not only cancer chemotherapy but a large component of therapeutic agents. They are also associated with
several implications of CNS disorders. It is still unclear that how these transporters efflux such a large number of
chemically unrelated drugs. Pgp and MRP, though having similar structural topologies show a large difference in
their substrates. In the present study, we have generated homology models of Pgp and MRP, and performed in-depth
analysis of substrate binding to these protein. The substrate interactions obtained by induced fit docking studies well
correlated with experimental data. To find out the reason behind immense substrate variation in Pgp and MRP we
performed mutation studies. The active site residues and residue on the translocation pathway of MRP were mutated
to corresponding residues of Pgp that had similar positions in 3D structure. The mutated structure was further
subjected to steered molecular dynamics to obtain identical 3D conformations of mutated residues. The MRP specific,
Pgp specific and substrate common to both were re-docked. We noticed several striking structural features which were
responsible for substrate non-specificity. A detailed description of distance correlation between active site residues,
chemical features responsible for substrate binding and cavity volume have been discussed.








Homology modeling and in silico docking of Trypanothione reductase of Leishmania
donovani for identification of prospective Antileishmanial drugs
Dr. Nandini Sarkar and Ritika Chauhan
Department of Biotechnology and Biomedical Engineering, NIT Rourkela, 769008
Leishmaniasis is one of the neglected tropical diseases which have proved it to be life threatening. There are
an estimated 500,000 new cases of VL and more than 50,000 deaths from the disease each year, a death toll
that is surpassed among the parasitic diseases only by malaria. This is caused by a protozoan belonging to
Leishmania species which is transmitted by the bite of a fly Female Phlebotominae i.e. sand-fly. There are
various types of leishmaniasis depending on the area of infection varying from normal infection to death
causing leishmaniasis. In Indian subcontinent its one of the major concerns because of higher drug
resistance towards the present drugs and higher toxicity. Among all the types of Leishmaniasis which affect
the Indian population Visceral leishmaniasis imposes highest menace and is still not having any precise
treatment. In India VL is caused by Leishmania donovani. The present study is based on finding the suitable
target for drug designing and finding its inhibitors to facilitate the further drug designing process against
L.donovani. Trypanothione reductase is one such enzyme which plays critical role in survival of the
protozoa by maintaining the redox balance. The structure of Trypanothione reductase is modeled and
validated and further in silico virtual screening has been done using AUTODOCK4 and AUTODOCK
VINA docking to find out inhibitors which can be well along used for drug designing.
Keywords: Leishmaniasis, Leishmania, Trypanothione, Trypanothione reductase, Homology modeling,
Autodock, Dock










Homology Modeling of Human CXCR2 Receptor: To Facilitate Design of Novel Potent Drugs
Sapna Rani, M. Elizabeth Sobhia*
Department of Pharmacoinformatics
National Institute of Pharmaceutical Education and Research (NIPER),
Sector-67, S. A. S. Nagar, Punjab, India
*Email: mesophiaCniper.ac.in
Abstract:
Chemokine receptor type2 (CXCR2), a membrane bound GPCR, is a potential target for a variety of conditions like
inflammatory diseases, cancer, autoimmune disorders and Alzheimers disease besides angiogenesis and
hematopoiesis. Such a versatile use of CXCR2 necessitates the need to comprehend the 3D structure of this membrane
protein to better understand the binding modes of various agonists and antagonists. This is essential for the design of
more potent ligands. As the crystal structure of CXCR2 has not yet been resolved, we developed a multiple template
based homology model using CXCR1 as the primary template. A good quality Ramachandran Plot with reasonable
Errat Plot and Prosa energy alongside other vital analyses support the reliability of this model for use in designing
drugs targeted at CXCR2. Docking studies were then performed to characterize the probable active sites and the
binding affinity of the receptor with different potent ligands currently at the different stages of clinical trials. The so
obtained results are currently being used in the design of drugs targeted at CXCR2 for addressing various immune and
inflammatory responses implicated in myriad disorders.
Keywords: CXCR1, CXCR2, GPCR, Homology modeling, Docking.
References:
1. Park, S. H.; Das, B. B.; Casagrande, F.; Tian, Y.; Nothnagel, H. J.; Chu, M.; Kiefer, H.; Maier, K.; De Angelis, A. A.; Marassi,
F. M.; Opella, S. J. Structure of the chemokine receptor CXCR1 in phospholipid bilayers. Nature 2012, 491, 779.
2. Stadtmann, A.; Zarbock, A. CXCR2: From Bench to Bedside. Front Immunol. 2012, 3, 263.
3. Haldar, S.; Raghuraman, H.; Namani, T.; Rajarathnam, K.; Chattopadhyay, A. Membrane interaction of
the N-terminal domain of chemokine receptor CXCR1. BBA-Biomembranes 2010, 1798, 1056.

4. Singh, R.; Sobhia, E., M.; Homology modeling of human CCR2 receptor. Med Chem Res. 2011, 20, 1704.








Identification of potent inhibitors against FlgT from Vibrio cholerae by in silico modeling and docking
approaches
D. Sasikala and P. Srinivasan*
Molecular Biology Lab, Department of Bioinformatics,
Alagappa University, Karaikudi-630003, Tamilnadu, India
E mail: sri.bioinformatics@gmail.com
The motile bacterium of Vibrio cholerae, the causative agent of cholera, human diarrheal disease
acquired through contaminated food stuffs. The problem of such disease is faced by many countries for long
time. Vibrio cholerae has a locomotory organelle called filamentous flagella, helps in motility of cells. FlgT,
identified as a one of the novel motility gene responsible for cellular attachment and colonization. It also has
been proposed to be involved in flagellar formation at the basal body thereby anchoring cells to their
environment. Hence the effective inhibition of FlgT could be the most promising strategy in preventing and
treating infections. In order to find the structural aspects of target protein, MODELLER program was used
to built model with the help of molecular modelling approach in accordance with crystal structure of 3WIE
as template. The reliability and quality of the predicted model was analyzed by PROCHECK program was
prioritized for refinement through molecular dynamic simulation using GROMACS. Glide docking studies
were carried out for therapeutic target to identify lead molecules from the databases viz., Maybridge, Zinc,
Asinex, and Binding. Furthermore pharmacokinetic property was also analysed to obtain effective drug
candidates against target receptor. Consequently the binding ability of those identified lead compounds for
the specific target was validated by induced fit docking. Hence, the study could suggest lead compounds
selectively for inhibiting the potential target of FlgT results in destabilization of flagellum leads to partial
blockage of infectious process.

Keywords: FlgT, Vibrio cholerae, MODELLER, GROMACS, Induced fit docking.








Molecular modeling, Docking and Molecular dynamics study of Phospholipase A2
(PLA2)
Sathishkumar Chinnasamy and Karthikeyan Muthusamy*
Department of Bioinformatics, Alagappa University, Science Block, Karaikudi 630004
*Correspondence: mkbioinformatics@gmail.com
Abstract
The phospholipase A2 (PLA2) are present in snake venoms. PLA2 exhibit wide varieties of
pharmacological effects such as neurotoxicity, myotoxicity, cardiotoxicity, hemorrhagic, anticoagulant,
edematogenic and hemolytic. In this study, the three dimensional structure of phospholipase A2 of Naja
sputatrix (Malayan spitting cobra) was modeled through SWISS-MODEL, PRIME and MODELLER
program. The best model was selected based on overall stereo-chemical quality. Further molecular dynamics
simulation was performed to know the stability of the modeled protein using Gromacs software. High
throughput virtual screening was employed against binding and Chembridge databases. The top ten
compounds were selected based on the docking score and free energy binding calculations. These
compounds were analysed by Induced fit docking (IFD) and Quantum Polarized Ligand Docking (QPLD).
The ADME properties of these molecules were in acceptable range. Finally best three compounds were
selected based on the docking score and hydrogen bond interactions. Hence, these three molecules could be
selective potential inhibitors against PLA2.
Key words: PLA2, Molecular modeling, molecular dynamics simulation

















!omology modeling8 molecular dynamics8 e-p(armacop(ore
Mapping and docking study of 1*1M.C
%rs.#athi suganya-,S.Si,aranLani
*epartment o7 8ioin7ormatics, S#% 0$.)E#S.;T
" *isintegrin and metalloproteinase domain3containing protein?05"*"%?06 is cell sur7ace protein 9ith a
uni:ue structure possessing 8oth potential adhesion and protease domains. .n neurons, "*"%?0 is the
most important en2yme 9ith [3secretase acti,ity 7or proteolytic processing o7 the amyloid precursor
protein5"PP6 9hich plays a maLor role in al2himer=s disease and also responsi8le 7or $otch receptors and
tumour angiogenesis. /ence, it is essential to identi7y drug candidates that could potentially impede the
a8o,e mentioned disorders. /ere, 9e present the de,elopment o7 a homology model o7 "*"%?0 protein
using P#.%E 9hich re,eals &P.MR o7 8oth 7a,oured and allo9ed regions in ramachandran plot. ;he protein
modeled 9as optimi2ed 8y molecular dynamics simulation using *ES%>$*. Energy3optimi2ed
pharmacophore mapping 9as per7ormed using the Lunction peptides! then the Lunction peptides o7 a
nonstructural protein complex 9ere docked 9ith natural compounds .;he modeling studies conducted
shed light on the 8inding modes, and the critical interactions 9ith the peptides.

(ey9ords: /omology modeling , "*"%?0, P#.%E, %olecular dynamics simulation 5%*S6,*esmond,
E3Pharmacophore.


















Homology modeling, docking and molecular dynamic simulation to gain structural
insights of human Sodium-dependent glucose co-transporter 2 (SGLT2).
Sharat Chandra and Mohammad Imran Siddiqi
Molecular and Structural Biology Division, CSIR - Central Drug Research Institute, Lucknow 226 031, India

Sodium-glucose co-transporters (SGLTs) are responsible for renal glucose reabsorption, among them
SGLT2 performing most of this task and remainder by the SGLT1. Inhibiting this renal glucose
reabsorption, thereby leads to renal glycosuria. Therefore, such inhibitory agents potentially offer new
approach to the treatment of diabetes. Targeting SGLT2 inhibition is one of the most promising therapeutic
strategy because it is responsible for most of the renal reabsorption as it is expressed exclusively in the
kidney. In the present study, homology modeling was applied to predict the SGLT2 structure using Vibrio
parahaemolyticus SGLT protein as a template. The modeled structure not only highlighted the major
topological features of the Glucose and Sodium binding sites in the trans-membrane protein, but also
exhibited a common binding site for its substrate glucose and some potent inhibitors after performing
docking experiment. A molecular dynamics simulation has also been performed with glucose and Na
+
in
lipid bilayer which revealed that as Na
+
exit the Na site first, glucose undergoes significant fluctuation
within the binding pocket. Na
+
exit causes the conformational change in the segment of transmembrane
helixs, which may lead to the exit of glucose into intracellular space. Thus, with an extensive array of
information reported in the present study, on the transporter binding site, receptorligand interactions and the mode of
sugar transport, further structural insights on this important target may speed up the rational design of SGLT-2
inhibitors as anti-diabetic agents.













;E/E,19I+/ +@ * M+*E= @+, !-M1/ 55,6 5!EM+KI/E ,E5E29+, 9!,+-;! !+M+=+;H
M+*E==I/; 1/* I*E/9I@I519I+/ +@ 2+9E/9 I/!I?I9+,' ?H M+=E5-=1, *+5KI/; '9-*IE'

Su8hradeep Bhar-, Saura, %. )erma, Pinki #a9at
*epartment o7 pharmaceutical Science, Birla .nstitute o7 ;echnology, %esra, #anchi3O'P2?P, .ndia


1?'9,159: Binding mode analysis o7 some no,el 8en2opyran deri,ati,es as #P inhi8itors 9ere carried out through
molecular docking. ;he homologous three dimensional model 9as constructed through %>*E<<E# 5,&.?26 8y using
the x3ray crystal structure o7 human H#4 5pd8: '>*06 at 2.P U as template. ;his model 9as 7urther loop re7ined
and ,alidated using P#>/E( A E##"; programs. ;he optimi2ed structure sho9ed more than &OR residues in the
7a,ored region A additional allo9ed region o7 #amachandran plot, and no residue in the disallo9ed region. >,erall
@37actor o7 30.?P also suggest 7a,ora8le geometry and stereochemistry o7 the constructed model. "cti,e site 9as
predicted using *o@SiteScorer 9hich re,ealed di77erent ligand 8inding pocket through its dragga8ility score. ;he 8est
8inding site 9as selected 9hich consisted o7 C' atoms, ,olume o7 4PO U^, hydropho8icity raitio o7 0.O2. ;he
contri8ution o7 these sites to ligand 8inding and selecti,ity is cross3,alidated 8y molecular docking 9ith @lide ,P.0
5Schrodinger <<6 in sol,ated phospholipid 8ilayer en,ironment. ;he '*3picture o7 inhi8itor3protein complex
pro,ided signi7icant insights a8out the 8inding mode o7 no,el 8en2opyran deri,ati,es. ;hese results may leads to
de,elop ne9 #P antagonist as a /.)3? entry inhi8itor.

Keywords: homology modeling, #3P antagonist, docking, 8en2opyran deri,ati,e

NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN

















Modeling of three different conformational states of spo0F like protein involved in
Phosphotransfer Pathway in MCC0008 (Sample A).
Sandhaya S,
a
. Shaon Raychaudhuri
b
Ashoke Ranjan Thakur,
c


and Sujata Roy,
a*


,Rajalakshmi Engineering College, Thandalam, Chennai
a
, India
,
West Bengal University of Technology, BF-
142, Sector 1, Salt Lake, Kolkata, West Bengal, India
b
,and Techno India University, EM4/1, Sector V, Salt
Lake, Kolkata, West Bengal, India
c


Abstract:
Sporulation initiation phosphotransferase F, spo0F and Sporulation initiation phosphotransferase B was
searched in a strain of Bacilllus which is deposited at Microbial Culture Collection at the National Centre
for Cell Sciences in Pune, India and whose whole genome sequence has been determined and all contigs
annotated with RAST, we found two similar proteins: one is 89% and other is 59% similar using local
BLAST and local database. The sequence of these proteins were taken for homology modeling. The purpose
of this study has been to unravel the triggering of and correlation of quorum sensing induced sporulating
proteins. At least two types of environmental signals have been implicated in the induction of sporulation.
First, as the mass of a cell culture increases, certain secreted peptides accumulate in the extracellular
medium. When these peptides reach a critical concentration reflective of a particular population density,
they are sensed by cell surface receptors that are able to initiate a sequential transfer of phosphate groups
from ATP through histidine kinases (e.g. KinB, KinC) and two intermediate proteins, Spo0F and Spo0B, to
a transcription factor, Spo0A. A major role of phosphorylated Spo0A (Spo0A~P) at this stage of the life
cycle is to repress abrB, a gene that encodes an unstable repressor of numerous stationary phase genes, some
of which are required for sporulation. Spo0F and Spo0B are components of a phosphorelay that control
sporulation in the bacterium Bacillus subtilis through the exchange of a phosphoryl group. To describe the
conformational pathway of Spo0F, it is necessary to consider three distinct conformational states for Spo0F.
Here we have modeled all the three possible states of spo0F like protein from this strain using different
templates. The structure of complex of spo0F like and spo0B like protein were also modeled.

- Corresponding author













Homology modeling of msp7 like protein in Plasmodium falciparum A
potent target of malaria
SUPRIYA SRIVASTAVA PhD student Amity University
Malaria, a scourge of mankind, imposes a huge socioeconomic burden in tropical countries. Emergence of
multi-drug resistant malarial parasites impels us to explore novel drug targets. msp7 like protein is a
promising antimalarial drug target. Merozoite invasion of red blood cells is crucial to the development of the
parasite that causes malaria. Merozoite surface proteins (MSPs) mediate the rst interaction between
parasite and erythrocyte. In Plasmodium falciparum, they include a complex of products from at least 3
genes (msp1, msp6, and msp7), one of which, msp7, is part of a gene family containing 3 and 6 adjacent
members in Plasmodium yoelii and Plasmodium falciparum, respectively. The aim of the work is to give
structure msp7 like protein & to do docking studies employing synthetic and natural mol The msp7 like
protein of Plasmodium falciparum was characterized in silico and protein disorder was predicted using
available online tools. Since the crystal structure of msp7 like protein of P. falciparum is not yet available,
its three-dimensional structure was constructed by homology modeling using the Schrodinger software and
2AP3_A as a template. Energy parameters fell in thermodynamically stability zone. Modeled structure
revealed appreciable measures when validated. Ramachandran plot signified the present work undertaken
through conformational parameters (phi) and (psi) angles calculated from model with 83.2% residues in
most favoured region. Further PROCHECK results confirmed acceptance of model through main and side-
chain values. Structure of msp7 like protein can be important tool for structure based drug designing
techniques to impel the search of new efficient inhibitors.The virtual screening and docking studies with
synthetic & natural molecule is underway.














A server for classification of human hormones and Non-hormones
based on sequence derived parameters using artificial neural
network
Jigar Patel, Mickey Tiwari, Tejashri Dalvi
Department of Bioinformatics, G. N. Khalsa College, Matunga, Mumbai India.

Contact: jigar.patel3112@gmail.com, mickeytiwari1451@gmail.com
Abstract: The prediction of hormones and non-hormones from the protein sequences is a
tortuous task in bioinformatics as well as in wet lab techniques, both task are expensive and
time consuming. It has further become more important to classify as the number of
sequenced information grows exponentially over time and the need to classify remains
unsolved. We describe a novel approach for classifying the hormones and non-hormones
from mixed protein sequences using artificial neural network (ANN). The online server will
classify in 3 levels /steps in first level, the tool will predict query protein as hormone or non
hormone. If protein encountered is a hormone then in second level it will further classify
hormone into human hormones or Non human hormones and finally it will be compared with
the database of human hormones to predict its nearest proteins using blast algorithm. We
have used dataset of 156 human hormones, 958 non human hormones and 2953 non
hormone proteins for training set using Backpropagation algorithm. Validation was done
using various statistical methods like n fold cross validation, MCC, Specificity, sensitivity
and Q
pred
and accuracy was calculated at the end .

Keyword: hormone, non-hormone, Human Hormones, artificial neural network, multiple
Backpropagation, sequence derived features
Future aspect: we would be adding few modules that will make us classify the hormones
entirely (steroids included). And Offline version of this Server would be made in java to
expand its usability.











In-silico studies of drug agonists for modelled mutated Melanocortin4
receptors in the treatment of obesity
Sruthi Unni
National Institue of Technology, Rourkela.

Abstract
Stimulation of agonistic activity of the melanocortin 4 receptors (MC4Rs) found in the brain is important for
the reversal of hyperphagia and other related disorders leading to obesity. Mutated melanocortin receptors
were modeled using SWISS-MODEL web server that uses the homology modeling algorithm. The predicted
models were validated using PROCHECK and PROSA for their stereochemical quality. Drug agonists From
the DrugBank were screened based on their affinity for the MC4Rs and their drug likeness from MolSoft.
Steroid derivatives were found to possess good drug likeness quality and followed the Lipinskis Rule of
Five. These selected ligands were subject to an automated docking analysis into the various mutated MC4Rs
(rec-2, 3, 4A, 4B, 5, 6), using AutoDock Vina. The ligands with high binding energies were analyzed for
their interaction with the receptors, hydrophobic or hydrogen bonding. These ligands can be further used for
in vivo testing for the reversal of hyperphagic conditions in mice models and later in human models, which
can be included as a valid treatment option against obesity.

Keywords: Melanocortin 4 receptors (MC4Rs), obesity, agonist, modeling, screening.












Homology Modelling and Docking study of human analogue protein
ALKBH8 with their inhibitors.
Kaushal Kumar Sharma, Nutan Chauhan, Ambarish Sharan Vidyarthi*
Department of Biotechnology, Birla Institute of Technology, Mesra, Ranchi-835215,
Jharkhand,
India
ABSTRACT
Many researchers are focusing on the structural and functional analysis of ALKB
homologs. ALKBH8 is the one of the most important recently identified homologue protein
of E.coli ALKB in human and its expression found mostly in human bladder cancer
(urothelial carcinoma).It is predicted that it protects DNA and RNA from direct reversal
alkylation or methylation damage at the transcription site or replication fork of DNA
and prevents the replication of DNA in excessive amount, thereby preventing the
tumor formation. Due to many side effects and increasing risk of drug resistance, there
is an urgent need to identify new potent inhibitors against ALKBH8. In the present study, the
3D structure of human ALKBH8 was predicted in through homology modeling approach
followed by energy minimization. Further, virtual screening using Glide against the
database of drug-like compounds downloaded from Zinc database was performed in
order to find better lead compounds. We propose Mucic acid (ZINC 12359024) as the best
compound on the basis of its docking energy (Glide score: -13.535455). Further in
vitroassay of the selected lead compounds would help to understand the mechanism of action
of new potent inhibitors.
*Corresponding Author, Email: asvidyarthi@bitmesra.ac.in










Application of Homology modeling in Structure based Drug Discovery: Case study on MELK kinase
Riddiman
Computational methods are becoming very successful in modern drug discovery since these methods are
rapid, cost-effective and efficient. Majorly these methods are divided into ligand based and structure based
methods. Nevertheless the structure based methods are more precise; elucidate the structural insights and
yields diverse actives. The availability of structural information of biological macromolecules is inadequate
on comparison with sequence information which is a bottle neck in structure based drug design.
Complementary computational methods like homology modeling, threading and ab initio methods are
used to predict 3D structures of proteins. However the suitability of the models obtained from these methods
in the structure based drug discovery is quite challenging. In the present work we attempted to establish the
protocol in generating precise protein 3D models for MELK kinase. The generated models were able to
spike the actives from inactives and futher their binding affinities are well correlated with biological activity
which helps in ranking the hits in virtual screening.





















Target specific approach to angiogenesis: Homology modelling, site specific
mutagenesis and virtual screening of a novel protein kinase

Navaneetha Nambigari
1
, Rajender Vadaeja
2
and Uma Vuruputuri
2
*
1
Department of Chemistry, Nizam College, Basheerbagh, Hyderabad 500 001.
*
2
Current Address: Department of Chemistry, University College of Science, Osmania
University, Hyderabad 500 007, *E-Mail: vuma@osmania.ac.in, vuma1957@gmail.com

Cancer remains a major cause of death [1]. Treatment regimesmodus operandi is targeting nutrient
requirement of tumor which is highly dependent on angiogenesis. The process involves proliferation of
endothelial cells regulated by multiple signaling transduction pathways[2]. Current progress involves
targeting the protein kinases (PKA), such as target specific substrates and catalytic cycle intermediates of
PKA. The cAMP signaling pathway provides a variety of possibilities for such an approach [3]. The
serine/threonine novel type-IcAMP-dependent protein kinase (NN1) is engaged in the regulation of
angiogenesis (through the induction of VEGF) by regulating the cell proliferation, apoptosis, differentiation
and tumorigenesis [4, 5].

In the present study, comparative modeling method was used to generate the 3D structure of the NN1
protein. [6] The active site residues of the protein are identified and site specific mutagenesis was carried
using standard insilico procedures. The virtual screening studies were carried out to identify the lead
molecules, optimized and ADME properties predicted [7]. The identified molecules can act as novel
antagonists for cancer treatment.

Key words: Angiogenesis, cAMP signalling pathway,

References:
1. Andrew M.scott et al. (2012) Antibody therapy of cancer. Nature reviews Cancer, 12: 278-287.
2. BalazsDome, Mary J.C. et al.(2007) Alternative Vascularization Mechanisms in Cancer, Pathology and
Therapeutic Implications, The American Journal of Pathology, 170 (1): 1 15.
3. Kleppe R et al.(2011) The cAMP-dependent protein kinase pathway as therapeutic target: possibilities
and pitfalls. Curr Top Med Chem. 11(11):1393-1405.
4. Li X et al. (2011) PRKX critically regulates endothelial cell proliferation, migration, and vascular-like
structure formation. Dev. Biol. 356:475-485.
5. Zimmermann B et al. (1997) PrKX is a novel catalytic subunit of the cAMP-dependent protein kinase
regulated by the regulatory subunit type I.J. Biol. Chem., 274: 53705378












Structural and Functional Analysis of Butyryl Cholinesterase Mutants

R Ashwini, M Kirithika, M. Rajeswari and N Santhi


Department of Biochemistry, Biotechnology & Bioinformatics Avinashilingam Institute
for Home Science and Higher Education for Women
Coimbatore-641043, Tamil Nadu.


Cholinesterases are among the most efficient enzymes known. They are divided into two groups:
Acetyl Cholinesterase and ButyrylCholinesterase. Acetyl cholinesterase (AChE) involved in the hydrolysis
of neurotransmitter acetylcholine. Organophosphorous (OP) compounds/pesticides inhibit this role of
AChE; thereby affect the balance of acetylcholine in the neurosynaptic junction. ButyrylCholinesterase is
also called as Plasma cholinesterase, pseudo-cholinesterase, cholinesterase (EC 3.1.1.8.) is synthesized in
the liver. The enzyme consists of four identical subunits (574 amino acids each) and nine carbohydrate
chains, with a molecular weight of approximately 342,000. It contains two active sites, an anionic and a
catalytic. The physiological function of plasma cholinesterase is breakdown of certain drugs including
muscle relaxant drugs and break down of certain toxic compounds such as pesticide. BChE is inhibited after
ingestion of organophosphorus and carbamate pesticides. However, this enzyme is responsible for the
hydrolytic degradation of certain short-acting neuromuscular blockers. Several cases of prolonged
neuromuscular block have been reported following the administration of these muscle relaxants in patients
with an impaired activity of plasma cholinesterase. Several authors have reported that decreased BChE
activity is due to point mutation. And also Cholinesterase inhibitors have been widely associated with the
treatment of Alzheimers disease, based on the cholinergic hypothesis, glaucoma, Downs syndrome and
myasthenia gravis. ButyrylCholinesterase (BChE) has attracted much attention because it can scavenge
organophosphorous compounds or hydrolyses toxic esters such cocaine.

Therefore, the present effort is to model the mutant forms of BChE, to correlate the structural
changes and low BChE activity. Total of 35, mutants was collected from the literature to study the structural
changes; these mutants were modeled using wild type BChE (309M) by PRIME Module of Schrodinger
software.
Homology Modeling of Caveolin-1: A Bioinformatics Approach
towards Prostate Cancer Treatment

Uzma Khanam
1
, B. K. Malik
1
and V. C. Kalia
2

1
Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh.

2
Institute of Genomics and Integrative Biology, Delhi, Kh.uzma@gmail.com


Prostate cancer is the third most common cancer and the second leading cause of male deaths in
Western countries. Caveolin-1 (cav-1) is a potent target of prostate cancer. Cav-1 acts as an
androgen receptor co-regulator, and also associated with Akt activation. Cav-1 is overexpressed in
prostate cancer cells, and is associated with prostate cancer progression. The expression of this
membrane associated protein is upregulated in prostate cancer. Cav-1 is secreted by prostate
cancer cells and this secreted cav-1 can stimulate cell survival and angiogenic activities. Cav-1
also increases androgen receptor genomic activity and, cav-1 can manipulate rapid, non-genomic
androgen receptor signaling at the plasma membrane. The aim of this study is to build structure of
cav-1 and to perform docking studies, employing synthetic and natural compounds. In the present
study, Cav-1 was modeled using homology modelling based on the crystal structure of the
covalent complex between the Bacillus subtilis glutaminase YbgJ and 5-oxo-L-
norleucine.Template and target sequences shares 33% identity. Homology modelling was
performed using Schrodinger-Prime. Model was validated using different protocols. The
stereochemical quality of the modeled protein was assessed from Ramachandran validation score
for most favored regions (88.1%) and allowed regions (8.1%). Structure of cav-1 can be important
for structure based drug designing techniques for further drug discovery. The docking and virtual
screening with synthetic & natural molecule is underway.





COMPUTATIONAL MODELLING & ANALYSIS OF ERBB2 EXPRESSION IN
HUMAN GATRIC TISSUES


G.Arthi, Banusree C & Yamini K
Department of Biotechnology,
Vinayaka Missions Kirupananda Variyar Engineering, College, Salem.




Gastric adenocarcinoma is a progressive disease that involves various distinct but overlapping stages. As
gastric niches are highly proliferate marked with constant cellular turnover, tumors arising in this
environment can be due to the accumulation of mutations in the progenitor or residual stem cells. The
protein ERBB2 (also known as p185, p185neu, c-erbB-2, and Her-2/neu) acts as a tyrosine kinase receptor,
stimulating cell proliferation; it is potentially involved in the growth and progression of malignant cells. We
sought to study the expression pattern of ERBB2 in Normal, chronic gastritis, intestinal metaplasia,
dysplasia and adenocarcinomatous tissues of the stomach. Thus from our study ERBB2 might serve as
potential targets to intervene in the Neoplastic transformation cascade of human gastric tissues. Henceforth
we thought to find out the structural predictions of the proteins in the various developmental stages of
tumours. Moreover we planned to work further on Proteins structural prediction, comprehensive modelling
and further advanced tools given in Schrdinger.
Keywords: Gastric adenocarcinoma, ERBB2, Human gastric tissues, Structural, tools.
.


Analysis and identification of -neurotoxin resistant mechanisms among sensitive and
resistant muscle nAChR Variants
Gunasekaran D
1
, Sridhar, J
2,*
, Ramasamy S
1,*
, Manimaran NC
2
, Saibabu
Thokala
1
,Krishnamurthy N
1
1
Cardiac Hypertrophy Laboratory, Department of Molecular Biology, School of Biological Sciences, Madurai
Kamaraj University, Madurai - 625021, India
2
UGC-Networking Resource Centre in Biological Sciences, School of Biological Sciences, Madurai Kamaraj
University, Madurai - 625021, India.
*
Correspondence: jsridhar@nrcbsmku.org A su88iahr@nrc8smku.org

Snake bite is one of the major socio-economic problems in developing countries like India. The
snake -neurotoxins act by binding to the muscle nicotinic acetylcholine receptors (nAChRs) in the
postsynaptic membrane of skeletal muscles and prevent the binding of acetylcholine, thereby blocking the
excitation of muscles. Interestingly, some animals like Mongoose (Helogale parvula), cobras (Naja sp.),
hedgehog (Erinaceus concolor) have natural resistance against snake -neurotoxins. These animals were
shown to have high levels of variations in the -neurotoxin binding sites of nAchRs. The ligand biding site
of the nAChR was found within a short peptide pocket of a subunit that includes the tandem cysteine
residues at the position 192 and 193. In this, particular stretch mongoose and humans have seven amino acid
difference. Five out the seven residues are clustered in the presumed ligand binding site, close to cysteines
192 and 193. So, this study is aimed to elucidate the molecular basis of acetylcholine receptors binding
mechanism of -neurotoxin using computational analysis. In this study, we have chosen various alpha
neurotoxins [Bungarotoxin (-BTX) and cobratoxin], agonist (acetylcholine) and various competitive
antagonist ligands to identify their mode interaction within the ligand binding sites. The human and
resistant animals nAChR protein was modeled using prime with appropriate template. Then each subunits
were assembled using coot-crystallographic tool. Then HADDOCK server was used to perform various
protein-protein docking analysis among resistant and sensitive animals using nAChR and -BTX. Further
membrane protein(nAchR BTX) molecular dynamics were carried out using Desmond tool in
Schrodinger suite. The various analysis were performed for to identify ligand binding pockets of various
agonists and antagonists in nAChR. We believe, understanding the resistance mechanism of nAChR variants
will give clue for the development of novel competitive agonist against the -neurotoxins.

Structural similarity based prediction and validation of Dengue virus host
interactions with respect to domain III envelope glycoprotein

J. Asnet Mary
1
, R. Shenbagarathai
2


3. Department of Zoology, Fatima College, Madurai, Tamil Nadu, India
4. PG and Research Department of Zoology and Biotechnology, Lady Doak College, Madurai,
Tamil Nadu, India.
Virus-host interactions are commenced at the entry level by binding of the envelope glycoprotein to
the surface receptor proteins of the host cell. Domain III envelope glycoprotein of Dengue virus binds to the
receptor proteins of the host. But, the receptor proteins of Dengue virus are still remaining unexplored. As
viruses have limited genes, it mostly relies on host factors to favour viral binding and pathogenesis. Hence,
the structural similarity based computational method was adopted in identifying the receptor proteins of
dengue virus. The host proteins that have structural similarity with the domain III envelope glycoprotein in
its three dimensional structures are identified. The functional partners of those proteins were identified and
validated by Gene Ontology and literature search. It was found that the domain III envelope glycoproteins
are structurally similar to human proteins such as fibronectin and tenesin that use integrins as receptors.
Hence, human integrin may act as a receptor for Dengue virus as it shares structural similarity with integrin
ligands. This computational prediction provides an additional tool for understanding the virus-host
interactions and helps to identify potential targets in the host. Further, it warrants wet laboratory
experiments for the development of effective antiviral compounds.













PEPTIDE THERAPY FOR CANCER TREATMENT: AN INNOVATIVE MILESTONE IN
CANCER THERAPY
Aravind Setti, S Srikannth, P Deepthi, Smita C Pawar
Dept of Genetics & Biotechnology, Osmania University, Hyderabad - 500007
aravind@osmania.ac.in, Mobile: +91-9948605060

Despite improvements in cancer therapies over the time, metastatic solid cancers remain largely
incurable, and the survival for patients with these malignancies is often measured in months. In this era of
targeted therapies, substantial efforts are being made to identify the optimal target for each type of cancer.
There are ample genetic and laboratory studies on cell cycle pathways, cell survival pathways, Apoptic
pathways. However, these pathways are vital to the growth and survival of cancer cells. Inhibitors targeting
this pathway are entering the clinic at a rapid pace. Indeed, most of the inhibitors are failing at different
levels o clinical trials because, they lack proper ADME properties.
Interestingly, peptide therapy draws the attention of researchers in the treatment of cancer. For the
continuous growth and survival of malignant cell requires oxygen and nutrients that is supplied by blood. In
order to grow tumour blood supply is required that is provided by blood vessels. Interestingly, new blood
vessels are formed at this stage; the process is called Angiogenesis. In the course of angiogenesis new blood
vessels are formed by breaking the basement membrane of the cells. The anti-angiogenic, carboxy terminal
non-collagenous domain (NC1) derived from human Collagen type IV alpha 6 chain, [6(IV)NC1] or
hexastatin was reported and tested invitro on cancer cell lines.
Type IV collagen is the predominant collagen in vascular basement membranes of blood capillaries.
Arrestin, Hexastatin, canstatin, tumstatin and endostatin are novel basement membrane derived endogenous
inhibitors of angiogenesis. However, the mechanism of interaction is not yet been reported so far. Therefore
we are considering the proteins such as MMP2, MMP9, Laminin10 & MT1 MMP interactions in insilico
approaches by molecular protein-protein docking analysis and resultant peptides are cloned and expressed in
E.coli heterologous system. Purified proteins will be tested against cancer cell lines invitro. In conclusion
anti angiogenesis peptides are prepared insilico and molecular interacitons between basement membrane
proteins and angiogenesis inhibitor peptides will be docked and resulting molecules are tested on cell lines
invivo for further confirmation.










3D computational model of rice bran protease (RBP): First report of a protease with
cupin fold
Roopesh S and Purnima Kaul Tiku,
Department of Protein Chemistry and Technology
CSIR-Central Food Technological Research Institute, Mysore

The cupin super family is the most diverse class of proteins named on the basis of conserved -barrel fold
which comprises of both enzymatic and non enzymatic members. However, a protease belonging to cupin
super family has not been reported till date. In our earlier work a novel protease (RBP) was purified and
characterized from rice bran. Here, we are presenting the amino acid sequence of RBP which has been
deduced by in-gel trypsin digestion and MS/MS analysis. The 3D structure of RBP was predicted using
homology module of prime through the maestro interface of Schrodinger package. Docking was performed
using bioluminate integrated in the maestro. Putative active site residues were predicted in the modelled
structure using docked insulin B chain and neurotensin as substrate using Q-site. Elucidation of these
molecular characteristics will help in in silico screening and understanding the structural basis of substrate
binding to RBP and pave new ways to understand this unusual protein, further structure-function
characterization of RBP would reveal its physiological significance.


















Dimerisation of Horsegram Bowman Birk Inhibitor is guided by an intramolecular interaction in the
monomer.
Vinod Kumar
1
, Neha Vithani
2
, Balaji Prakash
2
and Lalitha R Gowda
1

1
Department of Protein Chemistry and Technology, CSIR-Central Food Technological Research Institute,
Mysore 570023.
2
Department of Biological Sciences & BioEngineering, Indian Institute of Technology, Kanpur 208016.
Legume seed Bowman Birk inhibitors (BBIs) that inhibit mammalian proteases associate and exist as dimers
in solution. Structure for horsegram BBI dimer was homology modeled using experimentally determined
crystal structure of winter pea seed inhibitor (PDB ID- 1PBI) as a template. An interesting interaction found
in the dimer model of the horsegram inhibitor is a knob-in-hole like interaction formed between Asp76 and
Lys71 at the C-terminus of the monomer. We postulated that this interaction stabilizes the conformation of a
loop at the C-terminus, which in turn enables a strong interaction at the dimer interface between Asp75 of
one monomer and Lys24 of the other monomer. This interaction appears to be responsible for stable
dimerization of the molecule. Accordingly, site directed mutagenesis followed by size exclusion
chromatography and SDS-PAGE demonstrate that mutation of either Lys71 or Asp76 compromises
dimerization and leads to the formation of a monomer, which is kinetically similar but less thermo stable
than the dimer. Molecular dynamics simulation carried out on the dimer model for horse gram inhibitor
reveals that this knob-in-hole interaction is stable in solution. In contrast, the intermolecular interaction at
the dimer interface is initially destabilized due to a side chain orientation of Asp75. However, the interaction
is reformed once the conformation of Asp75 side chain reorients and gets stabilized. Biochemical studies
further validate this model; as a double mutant of horsegram inhibitor-K71D/D76Kwhere the loop forming
residues are interchanged, renders the molecule a stable dimer. Overall, the C-terminal knob-in-the-hole
interaction appears to be a lynchpin, which mediates the specific interaction between two monomers
resulting in the dimerization of the inhibitor.













Identification, Structure Prediction and Protein-Protein Interactions of RNA
binding proteins involved in Gene Silencing Mechanisms of Neurospora crassa
Kunal Zaveriand Dr.P.Kiranmayi
Department of Biochemistry, Institute of Science, GITAM University, Visakhapatnam-
530045.
Abstract
RNA binding Proteins (RBPs) influence the structureand function of RNA, and play a key
role in their synthesis, stability, transport, function and localization. They are the
heart of many processes like transcription, translation, cell cycle, and silencing
mechanisms. Understanding the functions of RNA Binding Proteins(RBPs) in Neurospora
crassahelps us to distinguish their targets from non-targets in vivo to perceive the genome
defense systems in Neurospora like Repeat Induced Point (RIP) mutations, Vegetative
Incompatibility (Quelling) and Meiotic Silencing. In the present study, a total of 313 RBPs
in Neurospora crassa, were identified using BLAST search with respect to their
homologouscounterparts and the resultant proteins were further classified on the basis
of RNA Binding Domains
(RBDs). The RBPs related to the genome defense mechanisms in N. crassa were considered
for the further study. Their interactions were analyzed using STRING database and
their structures were predicted by Bioluminate (Schrodinger) with homology modeling
approach and the resultant structures were validated using online tools. The binding sites
and proteinprotein interacting regions for the modeled proteins were identified using
Bioluminate. On the basis of the protein-protein interactions results and the available
data from the set of considered articles, an effective genome defense mechanisms in N.
crassawere designed. This study also provides important insights into how the RBPs
function in Neurospora in general








Probing into Protein Binding Sites:
A Sequence and Structural Design Perspective

Dighe A., Chandra N.
1
, Vishveshwara S.
2
, Ananthasuresh G.K.
3

1
Department of Biochemistry, New Biological Sciences, Indian Institute of Science, Bangalore-560012
2
Molecular Biophysics Unit, Indian Institute of Science, Bangalore-560012
3
Department of Mechanical Engineering, Indian Institute of Science, Bangalore-56001
ABSTRACT:
Present day biology necessitates an understanding of the molecular basis of recognition between
proteins and their associated ligands. Identification of local similarities within protein binding sites brings out
functional relationships among proteins. Following the notion that proteins with similar biochemical function possess
similar binding pockets for a ligand, we probe whether this similarity in the immediate vicinity of a ligand extrapolates
to regions around the binding site. For this purpose we consider the region upto 4.5 from each atom of the ligand as
the binding site (termed as Zone1), and another region surrounding Zone1 upto a distance of 4.5 (termed as Zone2).
This region i.e. Zone2 excludes those amino acid residues which are present as a part of Zone1. A dataset comprising
of 18895 binding sites from 16095 proteins is used. Sub-structure similarity among ligand binding sites (i.e. Zone1)
and their corresponding Zone2 is assessed by means of an in-house algorithm, PocketMatch. Similarities obtained are
found to be statistically significant by formulation of p-values. Quantification of such binding site similarities is
screened for false positives by generation of decoy sites. Local similarities are seen to exist in the immediate vicinity
of a ligand i.e. among Zone1 regions. Such similarities are observed to extrapolate further into the protein structure to
regions surrounding Zone1 (i.e to Zone2), for proteins belonging to diverse folds. Quantification of such similarities
yields insights about the nature of those regions surrounding a binding site, if two proteins are said to have similar
binding sites. Such regions may be crucial to maintain the structural integrity of a binding site and could aid in optimal
binding of a ligand molecule. These constraints imposed by binding site architecture could be incorporated into the
design of sequences which fit a particular protein topology, such that the nature of the binding site is restored, or to
engineer novel binding sites on






TRAF6 Inhibition: A new paradigm for endotoxin neutralization
Bharath B.R
a
and Manjunatha H
a
*.
a
Department of PG studies and research in Biotechnology and Bioinformatics, Jnanasahyadri,
Shankaraghatta, Shivamogga 577451, Karnataka, India.
* For Correspondence,
Dr. Manjunatha H, Assistant Professor, Department of PG studies and research in
Biotechnology and Bioinformatics, Jnanasahyadri, Shankaraghatta,
Shivamogga 577451, Karnataka, India. Email: manjunatha75@gmail.com
Phone: +91 8105580506

Abstract
Infection begins when an organism successfully colonizes by entering the body, growing and multiplying.
Gram negative bacterial colonization causes a strong systemic immune response up on releasing
Lipopolysaccharide (LPS) into bloodstream. It induces the production of inflammatory cytokines. The
proponents of this hypothesis assume that some degree of systemic inflammation is a frequent response to
local infection and that intravascular responses to circulating bacteria and/or LPS often precipitate organ
failure and shock. In that concern the work has been designed to understand the signaling triggered against
LPS infection and to identify the potent target that neutralizes the LPS. The interconnection of pathways and
the regulation of proteins in a pathway were to be explored, so the Protein Interaction Network (PIN) in
macrophage as response to LPS is designed in silico and genomics of interactive partners in the PIN is
analyzed. PIN analysis proposed TRAF6 as potent drug target for LPS neutralization, though in silico
approaches identifies a target the target was validated by in vitro methods.
Keywords: LPS, PIN, In silico, In vitro and TRAF6.










SNP analysis of CAMP-GEFII gene associated with Polycystic Ovarian Syndrome

J.suganya
1
, M.Nishandhini
2
and Radha Mahendran
1*


Department of Bioinformatics, Vels University,Chennai -600117

ABSTRACT:
Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of
many complex human diseases. In this work investigation of polymorphisms in CAMP-GEFII was done to
determine if the genetic variation that can alter the expression and the functional gene to polycystic ovarian
syndrome (PCOS) using computational methods .CAMP-GEFII gene has been reported as a candidate gene
for (PCOS) based on linkage and association studies. CAMP-GEFII nucleotide and protein sequence (length
412225 bp and length 1011 aa) were retrieved from the NCBI database. From Pfam database the 60020
domain have been identified in CAMP-GEFII protein. There are 193 SNPs for this gene. Two
nonsynonymous SNPs, namely rs17853965 and rs17852173, were taken for analysis. Using a sequence
homology-based Sorting Intolerant from Tolerant (SIFT) server we have searched for the SNPs, which show
non-synonymous polymorphism between L647I and H679P were found to be deleterious. The nsSNP
Analyzer tool the variation L647I and H679P was analysed, where as L647I change was neutral and H679P
causes disease. Using PANTHER for evolutionary analysis of coding SNP H679P shows deleterious effect
on protein function. The genetic association database results showed that CAMP-GEFII II SNP (H679P) are
linked to PCOS coming under the disease class of metabolic disorders among the two nsSNPs, H679P was
identified as deleterious, reducing the protein stability of CAMP-GEFII. Hence, these SNPs can be used for
the larger population-based studies of female PCOS.
Keywords: CAMP-GEFII gene, polycystic ovarian syndrome, single-nucleotide polymorphism analysis













5-Aminosalicylic acid suppresses crucial cytokines responsible for aggravating
immunological condition in Allergic Asthma.
K.Rama Satyanarayana Raju, Saurabh Gupta, Kannan Elango, M.N.Sathish Kumar, Nilesh Ambhore,
Shashank M.
(JSS College of Pharmacy, Rocklands, Udhagamandalam, Nilgiris, Tamilnadu 643001)

Introduction:
Cytokines, mainly TNF-, IL-6 and IL-13 play an important role in regulating the immunological changes
during allergic asthma. TNF- activates transcription factors like NFB leading to synthesis of various
cytokines. IL-6 is responsible for recruiting neutrophils and amplifies the inflammatory response. IL-13
helps in switching B cells resulting in the formation of IgE bodies.
To evaluate the cytokine suppression activity of 5-Aminosalicylic acid (5-ASA) and its active metabolite N-
Acetyl 5-aminosalicylic acid (N-acetyl 5-ASA) in silico and in vivo with mechanistic correlation in allergic
asthma.
In-silico docking studies were performed for 5-Amino salicylic acid and its active metabolite N Acetyl 5-
Amino salicylic acid with target proteins by Glide version 9.3 of Schrdinger suit on windows 2007
workstation as operating system. The X-ray crystal structure of proteins, TNF - (PDB ID: 2AZ5), IL - 6
(PDB ID: 1N26) and IL - 13 (PDB ID: 3LB6) were obtained from RCSB Protein Data Bank
(http://www.rcsb.org/pdb). The docking results revealed that the molecule (5-ASA) and its active metabolite
(N-acetyl 5-ASA) formed H-bond interactions with the targeted receptors. Later allergic asthma was induced
in Balb/c mice using ovalbumin as allergen. In-vivo studies revealed potential baseline readings which were
significantly reversed in the animals treated with 5-ASA at tested dose levels. Total and differential cell
counts were regulated to normal in the animals treated with 5-ASA. TNF-, IL-6 and IL-13 levels were
significantly reduced when treated with 5 ASA. Later, in silico and in vivo correlation has revealed that the
suppression of TNF- and IL-6 levels were due to 5-ASA and suppression of IL-13 was due to its active
metabolite (N-acetyl 5-ASA).
From the observed results it is concluded that 5-ASA shows immunoregulatory activity by suppressing the
crucial cytokines involved in the pathophysiology of allergic asthma








9ypes and num)er of unique protein fragments t(at e4ist in nature
*r. #oshan %akam, (esha,a %. Biotechnology *epartment PES .nstitute o7 ;echnology
?00 Feet #ing #oad, BS( '
rd
Stage Bangalore G PM0 0OP
Email: m,rmakam@pes.edu

1)stract: Proteins are u8i:uitous in nature. .t is 9ell kno9n that these proteins are made up o7 20 amino acids
arranged in se,eral di77erent locations along the primary se:uence. ;o this day it has not 8een esta8lished 9hat
types o7 se:uences or 7ragments and ho9 many o7 these 7ragments exist in nature. ;his 9ork attempts to
accomplish this 8y 7irst determining the type o7 7ragments that exist theoretically and a 7ormula is arri,ed at that can
pro,ide 9ith the num8er o7 a particular type. ;he types o7 7ragments that can exist is 8ased on the length o7 the
7ragment, i.e., ', 4, P, ..., 4?. For a 7ragment o7 length ', the types o7 7ragments that can possi8ly exist are ' o7 the
same type, 2 o7 the same type and ? 8eing di77erent and all the ' can 8e o7 di77erent types 9ith the total num8er
8eing 20, ??40 and MO40 respecti,ely gi,ing a total num8er o7 O000 arrangements. ;his type o7 arrangement can 8e
extended up to length 4?. ;he length 4? is chosen such that there are 20 di77erent amino acids that can 8e arranged
on either side o7 an amino acid 9ith the amino acid 8eing placed at the center o7 7ragment length 4?. From the
Protein *ata Bank, protein se:uences are 7ragmented into di77erent lengths till 4? and do9nloaded into a data8ase.
;he types that can exist in nature although not in its entirety are then determined 8y comparing the 7ragments in the
data8ase to that o8tained theoretically. ;his 9ork attempts to accomplish such a 7eat and determine the types and
num8er o7 7ragments that can exist in nature.
KEHI+,*': protein, 7ragment, arrangement, Protein *ata Bank, nature








Structural analysis of ATP-binding subunit of an ABC transporter from
Geobacillus kaustophilus

Manjula M.,
1
Pampa K.J.,
2
Madankumar S., and Lokanath N.K.
1*
1
Department of Studies in Physics,
2
Department of Studies in Microbiology, University of Mysore, Manasagangotri,
Mysore 57006, India
ABC (ATP Binding Cassette) transporters also known as traffic ATPases form a large family of integral membrane
proteins responsible for the translocation of a variety of chemically diverse substrates across lipid bi-layers of cellular
membranes of both prokaryotes and eukaryotes. ABC transporters contain four structural domains: two nucleotide-
binding domains that hydrolyze ATP (Adenosine Tri Phosphate), which are highly conserved throughout the family,
and two trans-membrane domains that provide a translocation pathway. In prokaryotes these domains are often
separate subunits which are assembled into a membrane-bound complex, whereas in eukaryotes, these domains are
generally fused into a single polypeptide chain.
We purified and crystallized the ATP binding subunit of an ABC transporter from Geobacillus kaustophilus.
And determined the X-ray crystal structure of ATP binding subunit of an ABC transporter at 1.77 resolution, using
MAD method.
ATP binding subunit of an ABC transporter forms a dimer consisting of two monomers related by a two-fold
axis. The protomer folds into two distinct domains. The overall structure of ATP binding subunit is similar to the
structure of histidine permease from Salmonella typhimurium. Conserved residue Asp159, interacts with the -
phosphate of ATP through a water molecule that occupies a position similar to that of the magnesium ion in the crystal
structures of Ras- GMPPNP-Mg and of the F
1
,-AMPPNP-Mg complex. Asp159, which is highly conserved in ABC
transporters, is probably the residue that interacts with the divalent cation during ATP hydrolysis, by analogy with the
process of GTP hydrolysis in GTPases.













Balancing anti-amyloid and anti-cholinesterase capacity in a single chemical
entity: In-silico drug design
P.Parasuraman*
a
, R.Suresh
a
, D.Premnath
b

a
Department of Pharmacy, FEAT, Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu-
608002
b
Department of Bioinformatics, Karunya University, Karunya Nagar, Coimbatore,
Tamil Nadu - 641114
E-Mail: pvpram@gmail.com
Alzheimers disease is currently consideration to be a complex, multi factorial syndrome, unlikely to arise as
of a single causal factor; instead, a number of related biological alterations are thought to contribute to its
pathogenesis. This may enlighten why the currently existing drugs, developed according to the classic drug
discovery paradigm of one-molecule-one-target, have turned out to be palliative. In light of this, drug
combinations that can act at different levels of the neurotoxic cascade offer new avenues toward curing
Alzheimers and other neurodegenerative diseases. In parallel, a new strategy is buddingthat of
developing a single chemical entity able to modulate multiple targets simultaneously. This has led to a new
paradigm in medicinal chemistry, the multi-targetdirected ligand design strategy, which has already been
successfully exploited at both academic and industrial levels. As a case study, we report here on 1-(5-(3, 5,
6, 7, 8-pentahydroxy-4-oxo-4H-chromen-2-yl) benzo[d]thiazol-2-yl)-3-(2-oxobutyl) urea, a new molecule
developed following this strategy. The in-silico prole of 1-(5-(3, 5, 6, 7, 8-pentahydroxy-4-oxo-4H-
chromen-2-yl) benzo[d]thiazol-2-yl)-3-(2-oxobutyl) urea demonstrates the suitability of the new strategy for
obtaining innovative drug candidates for the treatment of neurodegenerative diseases.
Key Words: In Slico, Alzheimers disease, Flavones, Multi-targeted.




1 :ava )ased ;-I for M+='*+5K
Sam &au( D. an% Gautham 4.
'entre of A%vance% Stu%y in 'rysta((o,raphy an% Biophysics, University of Ma%ras
'hennai 0## #?!, In%ia

Ie, in our la8oratory ha,e de,eloped a F>#;#"$ 8ased molecular docking method named %><S*>(. /a,ing
tested this method 9ith more than ?00 protein3ligand complexes 9e ha,e 7ound this method per7orming 8etter than
other docking methods like "uto*ock, @><*, etc., in terms o7 its exhausti,eness o7 search and computation time. ;o
make the program user37riendly and accessi8le to in general to the research community, 9e are de,eloping a
@raphical 0ser .nter7ace 5@0.6 7or %><S*>(. Ie ha,e used the +")" programming language. ;he de,eloped @0.
has a molecule 8uilder, a molecule docking tool, etc. E77orts are 8eing made to make this a 9e83accessi8le
application.




















STRENGTHS AND LIMITATIONS OF PI3K INHIBITORS: AN INSILICO ANALYSIS
Aravind Setti, S Srikannth, P Deepthi, Smita C Pawar
Dept of Genetics & Biotechnology, Osmania University, Hyderabad - 500007
aravind@osmania.ac.in, Mobile: +91-9948605060

Despite improvements in cancer therapies over the time, metastatic solid cancers remain largely
incurable, and the survival for patients with these malignancies is often measured in months. In this era of
targeted therapies, substantial efforts are being made to identify the optimal target for each type of cancer.
There are ample genetic and laboratory studies on cell cycle pathways, cell survival pathways, Apoptic
pathways. However, these pathways are vital to the growth and survival of cancer cells. Inhibitors targeting
this pathway are entering the clinic at a rapid pace. Indeed, most of the inhibitors are failing at different
levels o clinical trials because, they lack proper ADME properties.
Emerging data on cancer suggests targeted therapy is more promising and recent finding on PI3K-
AKT pathway uncovered the therapeutic applications of Phosphatidylinositide 3-kinase (PI3K) specific
inhibitors and broad spectrum inhibitors of PI3K, AKT and mTORC. Interestingly PI3K inhibitors have
more therapeutic significance and p110 and p110 catalytic subunits of PI3K are subject of this study.
Class I PI3Ks phosphorylate phosphatidylinositol 4,5-bis phosphate (PIP
2
) phospholipid on the plasma
membrane to form the secondary messenger phosphatidylinositol 3,4,5-tris phosphate (PIP
3
). PIP
3
recruits
AKT on plasma membrane and that is phosphorylated by PDK1 and mTORC2. Activated AKT translocates
to cytoplasm and nucleus to phosphorylate various downstream substrates that are implicated in the cell
growth, proliferation and apoptosis. PI3K-AKT pathway is extensively studied in many cancers and several
inhibitors target this pathway in different levels. PI3K inhibitors are widely studied and few of them are
under clinical trials. PI3K constitutes regulatory subunit and catalytic subunit and isoform specific inhibitors
of p110 and p110 catalytic subunits are more promising. Therefore in this study comparative analysis of
p110 and p110 broad spectrum and isoform specific inhibitors were reported with binding affinities.
p110 structure was prepared and active site residues and properties were illustrated with p110 analogy.
Pharmacokinetics of PI3K selected inhibitors were reported. Furthermore evolution of PI3K isoforms were
studied. These findings are helpful in developing isoform specific inhibitors of p110 and p110 catalytic
subunits.










LIGAND BINDING STUDIES OF IL6 PROTEIN RESPONSIBLE FOR RHEUMATOID ARTHRITIS AND
CHEMICAL ANALOGUES OF Vitex negundo
Center for Bioinformatics Studies Dibrugarh University Dibrugarh,India
Paran Sundar Das, Abhinab Roy ,Karna Singh Yadav,Bijita Banik, Kanak Chakraborty, Surabhi Johari,Subrata Sinha
subratasinha@dibru.ac.in

Abstract- Rheumatoid arthritis (RA) , an autoimmune disease in which the immune system attacks the bodys own
tissues as a result, fluids build up in the joints causing pain in the joints and inflammation. It has been discovered that
IL6 protein is responsible for regulation of immune response, e.g during infection and after trauma, especially burns or
other tissue damage leading to inflammation and pain. Therefore interaction of IL6 with potent inhibitors may reduce
the action of IL6 ,damage of bodys own tissue by immune system. Vitex negundo is used for the treatment of anti-
inflammatory disease, however how the components of the Vitex negundo functions is yet unknown. In this paper an
attempt has been made to establish the insilico interaction studies of chemical compounds of Vitex negundo with IL6
that is responsible for buildup of fluids in the joints causing pain and inflammation. We found that among the screened
7 components p-hydroxy benzoic acid has passed all the properties of drug and it is selected for interaction.

Keywords: Rheumatoid arthritis, IL6, Vitex negundo, p-hydroxybenzoic acid, Auto-immune .
















*evelopment of Electronic /ote)ook (E=/" for c(emistry8 using open
source tools3
9anmay ?aner7ee8 ?alac(andra ?andodkar8 'ud(akar H N 5(aitanya Kedari
"<(E% <"B>#";>#.ES <;*., $E #A* entre,
B3M4D?B, '
rd
Stage, Peenya .ndustrial "rea, Bangalore3PM00PM.
Electronic <a8oratory $ote8ook 9as 7irst introduced in late ?&&0=s replacing the age3old paper38ased la8oratory
note8ook. First generation systems 9ere non3in,asi,e to la8oratory operations. Scientists used tools 7rom di77erent
,endors to compile a 7ile, 9hich had rele,ant in7ormation a8out the experiment. "d,antage o7 these systems 9as
mainly in retrie,al o7 data to satis7y organi2ation=s legal counsel during patent 7iling.
Present generation o7 E<$=s are much more ad,anced as they ha,e in38uild capa8ilities o7 <a8oratories
.n7ormation %anagement Systems 5<.%S6 A Scienti7ic *ata %anagement Systems 5S*%S6. <.%S is used to track
9ork7lo9 in the la8oratory. S*%S is used to store ra9 data 7rom the instruments. %ain ad,antage o7 this system is
the 9ay data is reused 7rom other experiments. ;hese 7eatures reduce analysis time.
.n our la8oratory, 9e ha,e ten chemists A 7our 8iologists, 9orking to9ards deli,ery o7 $e9 hemical Entity
5$E6. For our small preclinical drug disco,ery setup, 9e decided to use in3house de,eloped in7ormatics systems to
support our drug disco,ery acti,ities. .n this process, E<$ 7or chemistry 9as the 7irst tool to 8e de,eloped. Ie chose
to integrate open source chemoin7ormatics tools to capture chemical reaction, calculate properties, create image o7
the compounds and to register compounds into corporate data8ase. .n the poster, 9e 9ill illustrate 7eatures o7 our
in3house E<$ related to reaction capture, Stoichiometry calculations, procedure 9riting using rich text 8ox,
integration o7 di77erent analytical data 7iles into one 7ile, corro8oration o7 experiments A registration o7 compounds.
Present capa8ilities o7 our in3house E<$ is superior to the earlier generation o7 E<$=s 8ut re:uires to some more
de,elopment 8e7ore it can catch up 9ith the 8est 7rom the ,endors.












In Silico Identification of Potential Drug Targets in Salmonella enterica serovar Typhi:
A Comparative Genomics Study of Metabolic Pathways
Yamini Chand and Md. Afroz Alam
Department of Bioinformatics, Karunya University, Coimbatore 641114, Tamil Nadu, India
E-mail: yamini.chand4@gmail.com

Increasing emergence of antibiotic-resistant pathogenic microorganisms has necessitated the search for
novel drug targets. Classical drug discovery techniques are expensive and time-consuming. In contrast,
advances in genome-sequencing projects of several infective bacteria, bioinformatics and cheminformatics
has revolutionalized microbial drug target identification via providing tremendous useful information. The
present study is aimed at identifying putative therapeutic targets by comparative proteome and metabolic
pathway analysis in Salmonella enterica serovar Typhi (S. Typhi) which is an etiologic agent of typhoid
fever in human beings. A similarity search between pathogen and host was carried out to identify non-
homologous proteins, the essential proteins that are important for pathogens survival were verified using
the database of essential genes, metabolic functional association studies of the essential proteins were
performed to analyze their respective pathways. In silico analysis identified 39 essential proteins of S. Typhi
that were non-homologous to human host. Pathway analysis revealed that 27 drug targets were enzymes,
seven were non-enzymes, and five were conserved hypothetical proteins. Furthermore, prediction of sub
cellular localization and drug prioritization of 27 proteins confirmed that the drug targets would be useful in
design and discovery of novel therapeutic compounds against typhoid. The approach enables rapid potential
drug target identification and hence, highlight the significance of in silico systematic drug target
identification in the post-genomic era.














Sketching Science with Schrdinger

S.Balaji
Department of Biotechnology, Manipal Institute of Technology, Manipal-576 104, biobalagi@gmail.com

Protein structures in PDB shoots up and entangle biologists into the structural fold. Scientific journals and
text books are abound with illustrations of macromolecular structures illustrating these rapid advances. The
understanding of the relationship between structure and function has been termed molecular 3D literacy.
Biomorphic representation of proteins conveys the functional information explicitly in an artistic way.
Sketching scientific data by these artistic forms presented herein, promotes the understanding of proteins
form and function. This would be of great help to the graduate students from various disciplines to
understand these biomorphic presentations to improve their molecular literacy. The results are conspicuous.























IMPROVED SMALL-MOLECULE INHIBITOR OF THE ZINC ENDOPEPTIDASE OF
BOTULINIUM NEUROTOXIN SEROTYPE A
S.JAYA BHARATHI,
BHARATHIDASAN INSITUTE OF TECHNOLOGY, ANNA UNIVERSITY, TIRUCHIRAPALLI-620 024
E-Mail: jayabharathisivaprakasam@gmail.com


Optimization of a serotype-selective, small-molecule inhibitor of botulinium neurotoxin serotype A
(BONTA) endopeptidase is a formidable challenge because the enzyme-substrate interface is unusually large
and the endopeptidase itself is a large, zinc-binding protein with a complex fold and based on the
computational results, it is hypothesized that introducing a hydroxyl group to the inhibitor could improve its
potency. Synthesis and testing of the hydroxyl-containing analog as a BONTA endopeptidase inhibitor
showed a twofold improvement in inhibitory potency with a small increase in molecular weight (16 Da).





















Computational repurposing and experimental validation of FDA approved drugs for HIF-Prolyl
Hydroxylase inhibition

Mahesh Kumar Teli and Rajanikant G. K.
School of Biotechnology, National Institute of Technology Calicut,
Calicut - 673601, Kerala, India

HIF stability and activation are governed by a family of dioxygenases called HIF prolyl-4-hydroxylases
(PHDs). It has been identified as a new target to augment the adaptive machinery that governs
cytoprotection in disorders associated with ischemia/reperfusion, inflammation and oxidative stress. The
present work plan aims at giving new purpose to some well-established FDA-approved drugs. Exploiting
drug polypharmacology to identify novel modes of actions for drug repurposing has gained significant
attentions in the current era of weak drug pipelines. Here, we propose that by combining the literature
survey, docking and manual interpretation altogether, we were able to perform virtual screening on FDA
approved drugs to identify potential PHD inhibitors. Upon screening of FDA approved drugs, a final set of 6
hits were selected for experimental testing. All the six drugs were divers and immune-blotting was carried
out to evaluate their ability to up-regulate HIF, in order to validate our hypothesis. Out of six, three drugs
showed significant up-regulation of HIF possibly by inhibiting the PHD. It is believed that the appropriate
use of the literature survey, docking, manual interpretation and experimental validation strategy in drug
design process should improve the ability to identify hits and confirm their potential to serve as basis for
drug repurposing.










Synthesis, In-Vitro, In-Vivo Evaluation And Molecular Docking Of 2-(3-(2-(1, 3-Dioxoisoindolin-2-Yl)
Acetamido)-4-Oxo-2-Substituted Thiazolidin-5-Yl) Acetic Acid Derivatives As An Anti-Inflammatory
Agents.
Anna Pratima Nikalje
a
, Nazma Hirani
a
, Mangesh S. Ghodke
a
, R. Nawle
b
, H. Une
c
, S. Bari
d
a
. Department of Pharmaceutical Chemistry, Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus,
Rauza Bagh, P.B. No. 33, Aurangabad-431001, Maharashtra, India.
b.
Department of Pharmacology, Government College of Pharmacy, Aurangabad-431001, Maharashtra,
India.
c.
Department of Pharmacology, Y.B. Chavan College of Pharmacy, Aurangabad.
d.
Department of Pharmaceutical chemistry,
2
.R C. Patel College of Pharmacy, Shirpur.
* Email: ana@k.st



A series of novel 2-(3-(2-(1,3-dioxoisoindolin-2-yl) acetamido)-4-oxo-2-phenylthiazolidin-5-yl) acetic acid
derivatives 5 (a-l) have been synthesized by cyclo condensation of (E)-N'-substituted
benzylidene/methylene-2-(1,3-dioxo isoindolin-2-yl) acetohydrazide 4 (a-l) with mercapto succinic acid , in
dimethyl formamide as solvent, using anhydrous zinc chloride as catalyst in Microsynth microwave reactor.
The synthesized compounds were evaluated for anti-inflammatory activity using in vitro and in vivo model.
Furthermore, ulcerogenic toxicity study was performed for selected compounds. All the compounds have
shown promising anti-inflammatory activity in both the models. Docking studies were performed to know
the binding affinity of these derivatives towards the human serum albumin (HSA).




















Design and Synthesis of some novel biologically active 3.5-disubstituted 1, 2, 4-triazole incorporated
2-mercaptobenzothiazoles
Naga Srinivas Tripuraneni*, Md Afzal Azam
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Ooty, Udhagamandalam, Tamilnadu

Inflammation though one of the innate immunity responses continues to be a challenge due to the complex
biological pathways. Due to dose limiting toxicities and ulcerogenic potency there is a lacuna of a suitable
anti-inflammatory drug and the further biochemical complexity and location of PDEs made it more difficult
for selective PDE inhibitors. Therefore, in an attempt to identify safe and potent anti-inflammatory drug
candidates novel drug like molecules were synthesized by linking 1,2,4-triazoles and 2-
mercaptobenzothiazoles.The potent molecules (Hits) virtual high throughput screening was performed using
Schrodinger Drug design Suite on PDE4B receptor. The crystal structure of PDE4B is obtained for RSCB
Protein data bank (PDB ID: 1XM4). Plausible compounds were identified (virtual hits). Molecular
modelling studies predicted that the compounds 5f, 5g, 5h, 5i and 5c possess good docking affinity with the
PDE4B receptor and further, these molecules were subjected to anti-inflammatory studies in rats by
carrageenan induced rat paw oedema model and further the ulcerogenic index is also calculated. The data of
docking study, anti-inflammatory study and ulcerogenic index will be presented.












STUDY OF 4-(ACETYL AMINO)-N-[2-(2,4-DIMETHOXYPHENYL)-4- OXO-1,3-THIAZOLIDINE-
3-YL] BENZAMIDE AND ITS DERIVATIVES AS POTENT INHIBITORS OF COX-1:
DISCOVERY OF NEW ANTI-INFLAMATORY DRUGS
Priyam Thakor
*
, AniLkumar N, Antriksh Patel, N.V.Kalyane, R.B.Kotnal
Department of Pharmaceutical Chemistry, BLDEAs College of Pharmacy, BLDE University campus,
Bijapur-586103, Karnataka, India

email: priyamthakor@gmail.com

The discovery of two forms of the cyclooxygenase enzymes, COX-1 and COX-2, and the development of
COX-2 specific inhibitors as anti-inflammatory and analgesics have offered great promise that, the
therapeutic benefits of NSAIDs could be optimized thorough inhibitors of COX-2. This research is focused
on the effect of the anti-inflammatory N-acetylcysteine (NAC) on the inhibition of prostaglandin E2
formation in activated monocytes by specific and non-specific COX inhibitors. We found that
lipopolysaccharide induced prostaglandin E2 formation was significantly reduced by rofecoxib and by
diclofenac, two NSAIDs.
The Ligand structure is 4-(acetylamino)-N-(2-(2, 4-dimethoxyphenyl)-4-oxo-1,3-thiazolidin-2-yl)
benzamide used in docking. Virtual screening was performed on the basis of structural similarities, research
isomers & conformers. If we are making structures in chemsketch then we save it in Extended mol. format
.Now, when the structure of ligand is drawn and saved to the disk then we open the software Open Babel
GUI 2.0.2 which is used to convert the Extended mol. files to pdb files. After converting pdb files, this file
will use for further work and analysis using Autodock 4.
Study of molecular docking of molecules, synthesize some new N-[2(4-methoxyphenyl)-4-oxo-1, 3-
thiazolidin-3-yl] pyridine-4-carboxamide. This compound was evaluated for their possible biological and
pharmacological properties. The compounds were characterized by their melting point, TLC, IR, NMR and
Mass spectral studies.
Docking was carried out for 4-thiazolidinone with conformers 4-(Acetylamino)-N-(2-(2,4-dimethoxyphenyl)-
4-oxo-1,3-thiazolidin-2-yl)benzamide and its derivatives show minimum Binding Energy Range -11.43 to -
3.36. The corresponding ligands which we have found out were matched for the Lipinskis rule of 5
parameters and the results showed that, the 20 molecules show some extraordinary results out of 500
molecules. All the synthesized compound have been evaluated for anti-inflammatory (in-vitro) studies the
test compound (N-[2(4-methoxyphenyl)-4-oxo-1, 3-thiazolidin-3-yl] pyridine-4-carboxamide) A
1,
which
showed inhibition of 82% of albumin denaturation compared to standard drug and the anti-inflammatory
(in-vivo) studies the test compound A
1
which show inhibition of 65% of edema compare to standard drug







In silico designing and validation of a potential small molecule inhibitor against AphB, a virulence
gene activator from Vibrio cholerae
Rahul Shubhra Mandal
1
, Atri Ta
2
, Mohsina Tasneem
1
, Santasabuj Das
1,2*

1
Biomedical Informatics Center,
2
Division of Clinical Medicine, National Institute of Cholera and Enteric
Diseases, Kolkata - 700010, India
Vibrio cholerae is the causative agent of cholera, a severe waterborne diarrheal disease. Worldwide, it
affects 35 million people and causes 100,000130,000 deaths a year as of 2010. Antibiotics are available
that decrease the disease severity and duration of cholera. However, search for alternative therapies are
important to avoid the emergence of drug resistance. Toxin-coregulated pilus (TCP) and cholera toxin (CT)
are the two major virulence factors that are critical for pathogenesis of V. cholera in humans. Their
expression is initiated at the tcpPH promoter by the AphA and AphB regulators. AphA is a winged-helix
DNA-binding protein that enhances the ability of AphB, a LysR-type transcriptional regulator (LTTRs), to
activate tcpPH expression. Like other LTTRs (TsaR and BenM), AphB also possess a ligand-binding pocket
at the interface of RD-I and RD-II regulatory domains (RD) consisting of residues important for the
regulation of tcpPH expression. Ligand binding is reported for TsaR and BenM, but there is no ligand
reported for AphB which may bind to its active site pocket. Here we have taken an in silico approach to
design a small molecule inhibitor of AphB that blocks the expression of tcpPH promoter. As there is no
previous knowledge about the small molecule ligand, we have used LUDI program of Discovery Studio 2.5
to generate a small molecule ligand, which fits best into the AphB active site and also interact with the
critical residues within the pocket that are important for its activity. Subsequently, this starting molecule was
used for screening various small molecule databases like PubChem, ZINC etc. to create a dataset of similar
molecules for the purpose of further screening. Virtual screening of these small molecules was carried out
using GLIDE 5.8 docking program integrated in Schrdinger suite 2012. The resulted molecules were
further shortlisted by analyzing the interaction with binding site residues and binding free energy. Finally
selected molecules were evaluated by Molecular Dynamics (MD) simulation in GROMACS and studied for
their inhibitory role in mice models. One of the molecules inhibited the colonization of Vibrio cholerae O1
biovar eltor str. N16961 in suckling mice intestine and helped them to survive by significantly reducing
diarrhoea. This molecule also reduced cholera toxin secretion by the above strain, which was proved by the
rabbit ileal loop assay.






Developing new leads as anti-tubercular agents that target novel biological target of
Mycobacterium tuberculosis
Ravindra D. Wavhale
a
, Premlata K. Ambre
a
, Raghuvir R.S. Pissurlenkar
a
, Dhiman Sarkar
b
, Manoj
Avaghade
b
, Evans Coutinho
a
*.
Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Mumbai-400098, India
a

CombiChem Bio Resource Center, Organic Chemical Division, National Chemical Laboratory, Dr. Homi
Bhabha Road, Pune, Maharashtra 411008, India
b.
Email:evans@bcpindia.org*
Tuberculosis (TB) has been declared a global health emergency by the world health organisation (WHO). In
the last decade, Mycobacterium tuberculosis glutamine synthetase (MtGS) a key enzyme for nitrogen
metabolism has emerged as a potential target. The majority of known glutamine synthetase (GS) inhibitors
are simple amino acid (glutamate) analogues e.g. methionine sulfoximine and phosphinothricin which are
non-specific and non-drug-like molecules. Out of three different substrate binding sites of MtGs, a
significant difference is found in the nucleotide (ATP) binding site of MtGS and human glutamine
synthetase (hsGS). This provides the best opportunity to design GS specific inhibitors against
Mycobacterium tuberculosis.
The available crystal structure of MtGS bound to ADP (PDB code 2BVC) and with inhibitors (PDB code
2WGS, 3ZXR, 3ZXV, and 4 ACF) gave the insights of ATP binding site, provided important information
regarding key residues necessary for binding of substrate and inhibitor with enzyme. Amino acids Ser
280
,
Lys
361
, Tyr
230
and Glu
214
involved in hydrogen bonding with the substrate and inhibitor. Based on this
information novel inhibitors were designed containing different heterocyclic cores like imidazopyridine,
benzimidazole, imidazole and pyrrolo[2,3-d]pyrimidin. Designed molecules were further selected for
synthesis based on their interactions with MtGS, binding energy scores and drug like properties. Structures
of synthesized compounds were confirmed by characterizing with
1
H NMR and IR. All of these molecules
were evaluated for in-vitro MtGS inhibition.









Dopamine--hydroxylase as a novel drug target for cardiovascular diseases: In silico dentification
and in vitro validation of novel inhibitors
Sanjay Kumar Dey
#
, B.K. Thelma
$
, Suman Kundu
#

Department of Biochemistry
#
and Genetics
$
, University of Delhi South Campus, Benito Juarez Road, New
Delhi 110021, India

Human dopamine -hydroxylase (hDBH), expressed in noradrenergic nerve terminals of nervous system as
well as in chromaffin cells of adrenal medulla, is a key constituent of catecholamine biosynthetic pathway.
As such DBH has been implicated as an important drug target, whose inhibition could help the treatment of
hypertension and cardiac heart failure. Since cardiovascular malfunctions are major causes of mortality and
morbidity in India and abroad, it is important to design novel drugs to treat the fatal disease. Existing DBH
inhibitors are too few, often result in side effects and are frequently non-responsive to specific population.
Structure based rational drug design has been elusive so far since no three-dimensional structure existed for
full-length hDBH. We have solved this problem by building an in silico model for hDBH that was validated
against experimental data (Kapoor et al., 2011, PLoS One). The model was thus used in Autodock, Raccoon,
Glide SP and XP software for structure based virtual screening against several small molecule databases
including Diversity sets from National Cancer Institute, USA, ZINC natural compound databases, SIGMA
Myria Screen Set, ChemBank and KEGG. The docked structures were then scored using Autodock, XScore
and Prime MMGBSA (Schrodinger Inc., USA). Results of the multi-software based virtual screen have
suggested 69 compounds as prospective inhibitors of DBH. The lead compounds were then tested in vitro
against purified bovine DBH (with 95% sequence homology to human DBH), with the known inhibitor
disulfiram as a positive control, revealing 3 compounds to be potent inhibitors of DBH. In silico
pharmacokinetic study using QikProp module of Schrodinger Inc., USA, has revealed 3 leads to be latest
generation of DBH inhibitors having very high cell permeability and inability to cross the Blood Brain
Barrier. Enzyme inhibition assays confirmed that these inhibitors had kinetic parameters suitable for in vivo
evaluation. The binding of the inhibitors to the enzyme were validated biophysically using UV-visible,
fluorescence and CD spectroscopy as well as ITC. Assessment of cellular tolerabilities and immune-
toxicities against these lead compounds has shown promising results motivating us to proceed towards their
evaluation in model animal systems. CombiGlide and Ligand Based Core Hopping (Schrodinger Inc., USA)
methods have been employed to optimize the lead compounds computationally, for further chemical
synthesis and in vitro testing.
Reference: Kapoor A.; Shandilya M.; Kundu S., Structural Insight of Dopamine -Hydroxylase, a Drug
Target for Complex Traits, and Functional Significance of Exonic Single Nucleotide Polymorphisms. PLoS
ONE 6 (10): 2011, e26509.







Modeling, Synthesis and Characterization of Phosphopentapeptide A candidate substrate for Assay
of Calcineurin
Saraswathi R, Harish B.M. Gopi A, Anushree and Devaraju K.S.
Dept. of Microbiology & Biotechnology, Jnana Bharathi Campus,Bangalore University, Bangalore- 560-
056
E-mail: ksdevarju@bub.ernet.in

The measurement of Calcineurin (CN) activity plays an important role in understanding the mechanism
underlying many pathological conditions like cancer, metabolic aberrations and neurodegenerative
disorders. Current assay methods for CN are relative measurements which involve the use of CN or protein
phosphatase inhibitors. Hence, there is a need of CN specific assay without employing inhibitors for protein
phosphatases. Therefore the current study focused on modeling specific phospho peptides generated from
protein kinase A regulatory sub unit type II and docking them with CN using Molgro Virtual Docking
software. Further the candidate phospho pentapeptide was synthesized employing Fmoc method, purified
over HPLC and characterized by MASS spectrometry. This phospho pentapeptide was used for in vitro
assay of CN by malachite green method and the results compared with R II peptide which is a conventional
substrate used for CN assay. Docking study results indicate that phospho pentapeptide has higher binding
affinity to CN compared to R II and therefore it was employed as a substrate in the assay system, the in
vitro studies provides comparable results with RII peptide by Malachite green assay method.

















LIGAND DOCKING AND FRAGMENT-BASED PHARMACOPHORE BIVARIATE APPROACH FOR SCREENING OF
POTENTIAL DENGUE VIRUS INHIBITORS
Sindhoora Bhargavi Gopala Reddy
1,2
, Koji Ichiyama
2
, Emelyne Quek Jiang Li
2
, Youichi Suzuki
2
, Geetha
Mahadevappa
3
, Naoki Yamamoto
2
, Haraprasad Nanjundappa
1*
1 Department of Biotechnology, Sri Jayachamarajendra College of Engineering, Mysore, Karnataka, India
2 Translational Infectious Diseases Laboratory, Department of Microbiology, Yong Loon Lin School of
Medicine, National University of Singapore, Singapore
3 JSS Hospital, Mysore, Karnataka, India
E-Mail: nharaprasad@hotmail.com
Dengue fever (DF) is a mosquito-borne viral disease, caused by the Dengue Virus (DENV), an RNA virus
of the family Flaviviridae. DF has neither a specific treatment nor a vaccine. Hence, there is a constant need
to find an effective drug/vaccine as 40% of worlds population is at risk of infection. Current practices in
screening compound libraries for drug candidates involve either high throughput cell or enzyme based
assays and/or in silico screening by receptor-ligand library docking. While the in vitro approach is time
consuming and labour intensive, the conventional in silico methods suffer from inaccurate and inconsistent
prediction of binding poses, and results that do not often translate when tested in vitro.
Here, we report an improved method of computational screening of an FDA approved compound library for
identification of probable inhibitors of dengue viral proteins. A site points-centered grid was constructed at a
potential drug-binding site in the DENV protease complex. Initial screening was performed by Glide HTVS
docking of the compounds in the grid, and the results were enriched by SP and XP docking. In a receptor-
focused approach, the library was subjected to a second screening, to filter conformers that matched the site-
specific fragment-based pharmacophore hypothesis by using the Energy-optimized Structure-based
Pharmacophore (e-PCP) protocol. In this, a diverse fragment library was docked in the same grid as the
initial screening to generate PCP features after volume clustering of the docked poses of fragments. These
PCP features were then ranked based on the Glide XP-derived energetic values for their constituent atoms,
and using the best PCP features; several hypotheses with different matching rules were generated. The
hypotheses were then screened against the library for matches, which were further overlapped with glide XP
output from the first screen to produce higher enrichment of leads. In vitro studies of these enriched leads
further showed promising results as inhibitors of dengue virus. Hence, this method is better suited for
screening than conventional docking strategy alone. Bivariate screening method effectively uses the
potentially best druggable features of the receptors to identify compounds that bind with high affinity, as
well as interact with the predicted critical pharmacophoric features of the receptor. Apart from that, the
method adopted in the study gave nearly 4.5 times better enrichment when compared with univariate
method. However, the robustness of the method still needs to be explored.








Molecular docking guided structure based design of novel HIV-1 entry inhibitors.
Ramakrishna Munnaluri, Sree Kanth Sivan, Radhika Vangala, Vijjulatha Manga*
Molecular modeling and Medicinal Chemistry Group, Dept. of Chemistry, Nizam College, Osmania
University, Hyderabad 500001.
HIV-1 cell entry is mediated by sequential interaction of envelope proteins gp120 with the receptor CD4 and
co-receptor CCR5/CXCR4 on host cell. Binding of gp120 to CD4 and co-receptor triggers the release of
HIV-1 gp41, which undergoes a large conformational change responsible for viral cellular membrane
apposition, thereby allowing entry of the viral genetic material into the cytosol. Inhibition of these events
can be exploited to develop new drug candidates against non-trivial protein targets. To design novel
molecules for HIV-1 entry inhibition, a computational approach involving molecular docking and protein
ligand interaction studies was carried out on HIV-1 gp120 and HIV-1 gp41. Initially receptor structures were
explored for determining active site. Reported inhibitors of HIV-1 gp120 were docked into CD4 binding site
of HIV-1 gp120 and inhibitors of HIV-1 gp41 were docked into the hydrophobic pocket of CHR coiling
domain of HIV-1 gp41. Glide XP mode was used for molecular docking, all the docked conformations were
analyzed and a relation between biological activity and Emodel of complexation was obtained. Further the
best docked molecule and most potent inhibitors were re-docked into the respective binding sites using
Induced fit docking (IFD) protocol. This gave us the insight on structural requirements for binding of
inhibitors to receptor. Based on these structural features novel molecules were designed and docked into the
receptor binding site using both docking protocol. Molecules with better interactions and binding affinities
on HIV-1 gp120 were synthesized and screened for their biological activity. Novel symmetrically N, N-
disubstituted urea and thiourea were synthesized using microwave assisted synthesis under aqueous
medium. Synthesized molecules were screened for their HIV-1 gp120 CD4 binding inhibition ability by
HIV-1 gp120 CD4 capture enzyme linked immunosorbent assay. Designed molecules were found to inhibit
HIV-1 gp120 CD4 binding in micro molar concentrations. Designed molecules for gp41 with better
interactions and binding affinities will be synthesized and screened for their biological activity.
NH NH
X
L L
FHC FHC
X = O or S L = Linker
FHC = Fused Hetrocycle
Designed HIV-1 gp120-CD4 binding inhibitors













Synthesis of Novel Pyrazole derivatives: An investigation on their ability to inhibit
Monoamine Oxidase (MAO)

A. Therasa Alphonsa
a
, C. Loganathan
a
, S. Kabilan
a

a
Department of Chemistry, Annamalai University, Annamalainagar, Chidambaram, Tamilnadu-608 002,
India.


Monoamine oxidases are widely distributed enzymes that contain a avin adenine dinucleotide (FAD)
covalently bounded to a cysteine residue. Many living organisms possess MAOs and in mammals two
isoforms are present, MAO-A and MAO-B, located in the outer membrane of the mitochondria. These two
isoforms are involved in the oxidative deamination of exogenous and endogenous amines, including
neurotransmitters, thus modulating their concentrations in the brain and peripheral tissues. The MAO-A
inhibitors (MAOI-A) are used as antidepressants, while MAOI-B are used in the treatment of Parkinsons
disease.To identify the novel MAO-A inhibitors, a series of selective pyrazole derivatives were synthesized
and docked with high resolution crystal structures of MAO-A isoform. Use of docking study approaches
are leading to a better understanding of the main binding interactions of several inhibitors at the enzymes
active sites, and have facilitated the interpretation of their structureactivity relationship

















SYNTHESIS, MOLECULAR DOCKING, AND EVALUATION OF SOME NOVEL ANALOGUE
OF N'-[SUBSTITUTED] PYRIDINE-4-CARBOHYDRAZIDES AS POTENTIAL THERAPEUTIC
AGENTS

Atre, N. M.
*1
; Mandlik, P. R.
2
and Khedkar, D. D.
3

1
Department of Bioinformatics, Shri Shivaji Science College, Amravati- 444603, Maharashtra
2
Department of Chemistry, Shri Shivaji Science College, Amravati- 444603, Maharashtra
3
Department of Botany, Shri Shivaji Science College, Amravati- 444603, Maharashtra

Email: neet3atre@gmail.com

The present work aims to synthesize some novel analogue of N'-[Substituted]Pyridine-4-
Carbohydrazides. The synthesized compounds were characterized by elemental analysis, physical and
spectral data (IR, 1HNMR). Literature survey shows its antiviral, antibacterial, antitumor and anti-
carcinogenic activities. Seven synthesized analogues of N'-[substituted] pyridine-4-carbohydrazides and 30
similar drugs available in public domain database were docked against the Quinolinate
Phosphoribosyltransferase (Qaprtase) from Mycobacterium tuberculosis (PDB ID: 1QPR) active site cavity
with favorable ligand-protein molecular interaction. Calculation of molecular properties, pharmacophore
patterns and ADMET properties using Schrodinger Maestro 9.4 suite for these analogues shows enhanced
pharmacological properties similar to available drugs.
Keyword: Carbohydrazides, Molecular Docking, ADMET



















DESIGN, SYNTHESIS, DOCKING, QSAR STUDIES AND ANTICANCER EVALUATION OF SOME
NOVEL BENZAMIDE DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS

Avineesh Singh*, Harish Rajak, Vijay Patel

Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur (CG)-495 009 India.
Email: avineesh26@gmail.com

Cancer is projected to become the leading cause of death worldwide in the year 2010, according to a new
edition of the World Cancer Report from the International Agency for Research on Cancer. All newly
synthesized compounds were characterized using IR,
1
H NMR, MS and elemental analysis followed by
evaluation of their cytotoxic activity by MTT assay on HCT-15 cancer cell lines. The docking and
QSAR studies of all compounds were performed using Schrodinger Suite Software 2012 employing the
Histone Deacetylase Like Protein (HDLP) obtained at 2 A resolution (PDB ID: 1ZZ1). All the synthesized
compounds have shown varying degree of anticancer activity in the range of 8.6 to 80 g/ml. Among all
the synthesized compounds, 7S was found to be most potent with IC
50
value of 8.6 g/ml showed significant
anticancer activity against HCT-15 cancer cell lines. The docking studies indicated that the 4-
methoxyphenyl derivative exhibited lower scoring energies suggesting favorable binding of these ligands to
the protein with reference to SAHA with hydrophobic and van der Waals interactions. The hydrogen
bonding interaction between the compounds and the amino acid residues at the binding pocket of HDLP
showed that presence of hydrophobic aryl ring and the benzamide groups with free amino moiety are
important for anticancer activity. The results of the docking studies co-related well with the biological
activity. As the synthesized 4-methoxyphenyl derivative exhibited significant anticancer activity, this class
of drug can be further explored to develop more potent anticancer agents. QSAR study for all synthesized
derivatives was carried out by using maestro, phase of Schrodinger suite 2012. All derivatives showed
significant anticancer activity. QSAR result for anticancer potential produced highly predictive model that
has excellent r
2
0.91.









In silico docking analysis of GC-MS derived compounds from Emilia sonchifolia (L.) DC against
Pancreatic cancer

Pratibha Prabhakaran
1
, P. Chella Perumal
1
, D. Sophia
2
and V.K. Gopalakrishnan
1

1
Department of Bioinformatics, Karpagam University, Coimbatore, Tamil Nadu-641 021

2
Department of Biochemistry, Jyoti Nivas Degree College,Koramangala, Hosur Road, Banglore-560095



Pancreatic cancer is the tenth most commonly diagnosed disease which is increasing in India and is
the fourth leading cause of cancer death in the United States. Emilia sonchifolia (L.) DC (Asteraceae) is an
edible plant used in the Ayurvedic system of medicine. Plants serve as sources of compounds that act a
potential therapeutic agent for treatment of various diseases. The utility of these plants and its scientific
validation might have an effective tool for the development of drug discovery. On this account the present
study aimed to analyze the presence of bioactive compounds in the n-Hexane extract of Emilia sonchifolia
(L.)DC by GC-MS analysis and to validate the activity of the compounds against pancreatic cancer targets
(AKT and mesothelin) through in silico docking method. The GC-MS result has shown totally 80
compounds present in the n-Hexane extract of Emilia sonchifolia (L.) DC. These compounds were subjected
to ADME properties prediction and molecular docking studies (using QikProp and Glide in Schrodinger
suite) with ATK and Mesothelin proteins which are over expressed in the pancreatic cancer. Molecular
docking studies revealed that 1-(3-methoxy-2-pyrazinyl)-2-methyl-1-propanone exhibits the highest docking
score on both AKT and mesothelin target protein compared with FDA approved drugs and other bioactive
compounds present in the n-Hexane extract of Emilia sonchifolia (L.). This study concluded that the
bioactive compound 1-(3-methoxy-2-pyrazinyl)-2-methyl-1-propanone may act as a good inhibitor for both
AKT and mesothelin target proteins in pancreatic cancer. Thus it may lead to the development of novel drug
against pancreatic cancer.

Keywords: Emilia sonchifolia (L.) DC , GC-MS, Pancreatic cancer, ADME, Molecular docking.


















Synthesis, evaluation and molecular docking study of some new p-aminobenzoic acid derivatives as an
antiamnesic and cognition enhancing agents
Saurabh K. Sinha, Sushant K. Shrivastava
Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutics, Indian Institute of
Technology, Banaras Hindu University, Varanasi, U.P. 221005, India.

Alzheimers disease is a progressive neurodegenerative disorder, characterised by selective loss of
cholinergic neurons and accumulation of -amyloid protein in the selective brain areas such as cortex and
hippocampus.
1
Loss of memory, cognitive decline, impaired performance of activities of daily life and
behavioural changes are hallmark of Alzheimers disease.
2
Patients suffering with AD have low level of
acetylcholine (ACh) and choline acetyltransferase (ChAT) in the cortex and hippocampus. In our earlier
studies, we have reported some new schiff bases, anilide, imide and semicarbazones of 4-aminopyridine for
their cognition enhancing, antiamnesic and anticholinesterase activities among which benzophenone and
imide derivatives were found to be highly significant. In continuation of our previous research work
3-5
we
have designed and synthesized some new semicarbazones of p-aminobenzoic acid and evaluated for
antiamnesic, cognitionenhancing and anticholinesterase activities. The results illustrated a significant
cognition enhancing effect on elevated plus maze model with a significant reversal of scopolamine-induced
amnesia. A significant inhibition in acetycholinesterase (AChE) activity by all the synthesized compounds in
specific brain regions that is, prefrontal cortex, hippocampus and hypothalamus was observed. The IC
50

value and selectivity of synthesized compounds showed a comparable activity of 19 (0.0460.016 M and
11.960.64), (260) with reference standard donepezil (0.040.012 M and 15.24 0.86 M), (381) for
AChE and BChE inhibition respectively. Its enzyme kinetic study revealed a non-competitive inhibition of
AChE (Ki = 0.032 0.014) and a competitive inhibition of butyrylcholinesterase (BChE) (Ki = 8.46 0.62).
Docking studies predicted the binding modes of these compounds in AChE and BChE active sites and
showed an affinity with the key peripheral anionic site residues Trp-286, Tyr-124 and Tyr-341 of AChE and
Leu-286 and Val-288 of BChE. All the computational study confirmed their consensual interaction with
AChE and BChE justifying the experimental outcome.
1. Gil-Bea, F. J.; Garcia-Alloza, M.; Dominguez, J.; Marcos, B.; Ramirez, M. J. Neurosci. Lett. 2005,
375, 37.
2. Mohamed, T.; Rao, P. P. N. Curr. Med. Chem. 2011, 18, 4299.
3. Sinha, S. K.; Shrivastava, S. K. Med. Chem. Res. 2012, 21, 4395.
4. Sinha, S. K.; Shrivastava, S. K. Bioorg. Med. Chem. Lett. 2013, 23, 2984-2989.
5. Sinha, S. K and Shrivastava, S. K. Bioorg. Med. Chem. 2013, 21, 5451-5460.






IN-SILICO DESIGN OF NOVEL SIRT1 INHIBITORS FOR TARGETING BENIGN PROSTATIC
HYPERPLASIA
Mallika Alvala
a,$*
, Ravi Alvala
b
, Madhu Babu battu
a
, Venkat Koushik Pulla
a
, Yogeeswari Perumal
a
,
Sriram Dharmarajan
a
.
a
Birla Institute of Technology and Science, Pilani-Hyderabad Campus,
Hyderabad-500 078, AP, India.
b
G.Pulla Reddy College of Pharmacy, Mehdipatnam, Hyderabad-500 028, AP, India
$
National Institute of Pharmaceutical Education and Research, Hyderabad-500 037, A.P, India
Homology model of hSIRT1 catalytic domain was prepared using Prime, module of Schrdinger and active
site was identified by sitemap program. With the aim to design novel small molecule SIRT1 inhibitors
against benign prostatic hyperplasia, high throughput virtual screening of in house database of ~3000
molecules was performed. Benzthiazolyl-2-thiosemicarbazone scaffold has been identified as lead scaffold
with highest docking score hence, a total of 16 derivatives (BH1-16) were synthesized and characterized. In
vitro hSIRT1 activity assay revealed the significant SIRT1 enzyme inhibition by compounds BH1 and BH13
with an IC
50
of 46.270.7M and 15.30.8M respectively. MTT assay of BH1-16 on different cancer cell
lines (K562, MDA-MB 231, LNCaP and PC3) confirmed the significant growth inhibition of LNCaP cells
by BH1 (IC
50
4.09 M) and BH13 (IC
50
5.07M) with no cytotoxicity on HEK293 cells. Mechanistic studies
of BH1 and BH13 on LNCaP cells, illustrate a dose-dependent increase in annexin V positive cells and
activation of Caspase 3, demonstrating the induction of apoptosis. A dose dependent decrease in transcript
levels of SIRT1, Prostate specific antigen and increase in protein levels of p53 indicate the SIRT1 mediated
apoptosis effects of BH1 and BH13. In vivo studies on testosterone-induced benign prostate hyperplasia in
male wistar rat, BH1 and BH13 showed significant decrease in hyperplasia and SIRT1 transcript levels
compare to positive control. In conclusion, the present study demonstrates the in silico designing
corresponds to the in vitro and in vivo potential effects of Benzthiazolyl-2-thiosemicarbazone derivatives
against benign prostate hyperplasia via SIRT1 inhibition.









Identification of Aurora kinase A Selective inhibitor through Structure-Based Virtual Screening
(SBVS)
Mohane S. Coumar,
a,*
Sailu Sarvagalla,
a
Vivek Kr. Singh,
a
John Tsu-An Hsu
b
and Hsing-Pang Hsieh
b,*

a
Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014,
India

b
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan
Road, Zhunan, Miaoli County 350, Taiwan, ROC
E-mail:mohane@bicpu.edu.in, hphsieh@nhri.org.tw

Aurora kinases have emerged as promising targets for cancer therapy because of their critical role in mitosis.
These kinases are well-conserved in all eukaryotes. The activity of Aurora kinases is regulated mainly by
phosphorylation and degradation. In many of human cancers its expression is up regulated thats make an
indication that these kinases are involved in cancer regulation.
In the present study, in-house HTS library (125,000 compounds) was screened in silico using two docking
programs: Glide XP and Libdock. From each docking experiment top scoring thirteen compounds were
prioritized and tested for Aurora kinase A enzyme inhibition. Two compounds, CSV0B000620 (Aurora A
IC
50
= 341 nM, Mol.Wt = 220.2, ligand efficiency (LE) = 0.52) and CSV0C013921 (Aurora A IC
50
= 852
nM, Mol.Wt = 254.1, LE = 0.44,) showed better inhibition against Aurora Kinase A enzyme. CSV0C013921
was also identified as aurora A selective inhibitor with less than 30.9% inhibition of Aurora B enzyme at 50
uM concentration. CSV0C013921 was subjected to Glide XP docking and MM/GBSA (PRIME)
calculations. Further detailed molecular dynamics simulation helped to understand the factors involved in
the Aurora A selectivity of the compound.
N NH
O
N
N
H
N
H
2
N
O
CSV0C013921
CSV0B000620










DOCKING STUDIES OF SOME NOVEL OXAZINE SUBSTITUTED 9-ANILINO ACRIDINE
DERIVATIVES WITH TOPOISOMERASE II, SYNTHESIS AND EVALUATION FOR THEIR
ANTI-TUMOUR ACTIVITY
R. Kalirajan
1
, Niroj Shrestha
2
, S. Sankar
1
and S. Jubie
1

1
Department of Pharmaceutical Chemistry,
2
Department of Pharmacology, JSS College of Pharmacy (A
Constituent college of JSS University, Mysore), Udhagamandalam 643001, Tamil Nadu, India
E-mail: rkalirajan@ymail.com, shreniroj@gmail.com

A series of some novel oxazine substituted 9-anilinoacridines were designed for docking studies towards the
key Topoisomerase-II (1ZXM) by using Schrodinger Maestro 9.3 version. The insilico ADME screening for
the compounds were performed by qikprop module of Schrodinger software. The oxazine substituted 9-
anilino acridine derivatives 5a-f had good docking scores against topoisomerise II compared with standard.
The compounds 5a-f with good Glide score were synthesized. The synthesized compounds were
characterized and conformed by IR, NMR and Mass spectroscopy. The 3D QSAR studies for synthesized
compounds were performed by PHASE module of Schrodinger software. The compounds 5a-f were
evaluated for their anti-tumor activity against Daltons Lymphoma Ascites (DLA) cell growth by invitro
method. It was revealed that these compounds exhibited significant anti-tumor activity. All the oxazine
substituted 9-anilino acridines have more significant CTC
50
(concentration required to reduce viability by
50%) value in the range of 96-365 g/ml. There is good correlation between docking and anti-tumor
activity.
















MOLECULAR DOCKING STUDY OF 4-THIAZOLDINONE DERIVATIVES AS INHIBITORS OF
HIV-RT AND VIRTUAL SCREENING


Anil kumar. N*, Priyam Thakor, B. Shivakumar, R. B. Kotnal
Department of Pharmaceutical Chemistry, BLDEAs College of Pharmacy, BLDE University campus,
Bijapur-586103, Karnataka, India


The generation of anti-HIV agents using structure-based drug design methods has yielded a number of
promising non-nucleoside inhibitors (NNIs) of HIV reverse transcriptase (RT). Recent successes in
identifying potent NNIs are reviewed with an emphasis on the recent trend of utilizing a computer model of
HIV-RT to identifying space in the NNI binding pocket that can be exploited by carefully chosen functional
group predicted to interact favourable with binding pocket residues. The NNI binding pocket model was
used to design potent NNIs against both wild-type RT and drug-resistant RT mutants. Molecular modelling
and score function were used to analyze how drugresistant mutations would change the RT binding pocket
shape, volume and chemical make-up, and how these changes could affect inhibitors binding. HIV-1(human
immunodeficiency virus type-1) is the pathogenic retrovirus and causative agent of AIDS. HIV-1 RT is one
of the key enzyme in the duplication of HIV-1. Inhibitors of HIV-1 RT are classified as NNRTIs and
NNRTIs bind to a region that is not associated with the active site of the enzyme. Within the NNRIs
category, there is a set of inhibitors commonly referred to as thiazolidinones derivatives. The present 3D-
QSAR study is an attempt to explore the structural requirement of thiazolidinones derivatives for anti-HIV
activity. Based on the structural and bio-data of previous thiazolidinone analogs, 3D-QSAR studies have
been performed with a training set consisting 500 molecules, which resulted in one reliable computational
model. It is shown that the steric and electrostatic properties predicted by in-silico drug designing and the
hydrogen bond acceptor, hydrogen bond donor and hydrophobic properties predicted and were related to
anti-HIV activity. The synthesis of 4-Thiazolidinone,3-(4-methylphentyl)-1,3-thiazolidin-4-one was carried
out by Microwave Irradiation of p-methyl aniline, Formaldehyde and thioglycolic acid. The target
compound was characterised by IR, NMR, and Mass spectral data. The compound was evaluated for anti-
inflammatory activity. The result of In-silico model and synthesised compound was compared and were
promising.











In silico design, synthesis and Antidiabetic evaluation of some novel DPP-IV inhibitors
Anjana.A.K, Sugun Kumar Sharma, Prasanth Francis, Dr.M.J.N. Chandrasekar.
Department Of Pharmaceutical chemistry, JSS College of pharmacy, Ootacamund, T.N

Amino acids can, under appropriate conditions, enhance insulin secretion from primary islet cells
and - cell lines. In periods of fasting or starvation, amino acid release from skeletal muscle (primarily L-
glutamine and L- alanine) may modulate glucagon release from pancreatic -cells, which subsequently may
influence insulin secretion from - cells. Dietary amino acids may also stimulate incretin release, e.g., GLP-
1, from intestinal L- cells and therefore stimulate insulin secretion via indirect mechanisms. The positive
effect of administration of two amino acids to insulin secretion in in vivo was reported in a recent clinical
assessment of the effect of leucine and phenyl alanine. Therefore bis amino acid peptidomimetics may prove
as a potent DPP-IV inhibitors which apart from acting as antidiabetic agents, render essential amino acids
after metabolism and directly or indirectly aid in the secretion of insulin and control the complications of
diabetes.
From four amino acids such as Glycine (Y), Alanine (Y
1
), Leucine (Y
2
), and Valine (Y
3
), some
dipeptides based on permutations and combinations along with attachment on both sides of dipeptide with
some heteroaromatic groups, were generated with a virtual library of about 300 molecules. The generated
library of 300 ligands was screened on in silico crystal structure of DPP-IV protein (PDB id- 3NOX)
obtained from protein data bank. The study was performed using glide extra precession mode of Schrdinger
software. From the obtained in silico results, best 20 ligands were shortlisted and were further subjected to
induced fit docking studies in comparison with four marketed standard drugs namely sitagliptin, vildagliptin,
saxagliptin and alogliptin. From induced fit docking studies the molecules which showed better results than
standard were selected for synthesis. The final compounds namely AGSS208, AGSS108 and AGSS109
were taken up for further in vitro DPP-IV inhibition assay using DPP-IV inhibition assay. All the three
molecules showed promising DPP-IV inhibition on in vitro studies. One of the synthesized DPP-IV inhibitor
(AGSS208) showed good in vitro antidiabetic potential.














Quinolines as anticancer agents: The probable candidates for HDAC inhibition
Aparna V. Chavan, Pooja U. Trivedi, Supriya S. Mahajan
C. U. Shah College of Pharmacy, S. N. D. T. Womens University, Juhu Tara Road, Santacruz (W),
Mumbai- 400049, India
E-mail: aparna387@yahoo.com

Aim: To design, synthesize and evaluate the anticancer potential of 4-amino-7-chloroquinolines.
Objective: Quinolines exhibit a variety of biological activities like antimalarial, anticancer, anti-tubercular,
etc. Extensive literature search shows that anticancer nature of quinolines is because of HDAC inhibition.
Hence, the objective of this study is to design, synthesize and evaluate 4-amino-7-chloroquinolines as
anticancer agents.
Experimental:
Designing of 4-amino-7-chloroquinolines: In silico drug designing and docking approach saves time and
money. Docking predicts the affinity of ligands for the target. Docking study was carried out by using the
software Glide from Maestro 9.3 of Schrdinger, USA.
HDAC inhibition: Flexible docking (Figure 1) was done on HDAC enzyme (PDB ID 1T69) using SP mode
and was compared with suberoylanilide hydroxamic acid (SAHA). Hundreds of 4-amino-7-
chloroquinolines were screened and few selected compounds were synthesized on the basis of G-score,
hydrogen bonds and Vdw interactions.
Synthetic Methodology: N-(Aminoalkyl)-4-amino-7-chloroquinolines and N-(aminophenyl)-4-amino-7-
chloroquinolines were synthesized on laboratory scale from 4, 7-dichloroquinoline. Various substituted
amides, amines, sulfonamides and dithiocarbamic acid alkyl esters were synthesized. Their structures were
characterized and confirmed by IR and
1
H-NMR spectroscopy, respectively.
Pharmacological evaluation: Acute oral toxicity studies were carried out as per the OECD 423 guidelines.
Anticancer activity was evaluated by SRB assay using MCF7 cancer cell line. Results & discussion:
Results of anticancer activity are encouraging. G-scores of the compounds were well correlated with their
anticancer activity. Thus, 4-amino-7-chloroquinolines can be a new class of anticancer compounds.










Design and Synthesis of new class of ErbB2 inhibitors 4-thiazolidinones by one pot
approach.
Ananda.H, K.S. Sharath Kumar, Harsha K.B, K. S. Rangappa
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore-06, India

The cancer chemotherapy has entered a new arena of molecular targeted therapeutics. The ErbB2
(also known as HER-2) receptor is a proto-oncogene associated with a poor prognosis in breast cancer.
Herceptin, the only humanized anti-ErbB2 antibody currently in clinical use, has proven to be an essential
tool in the immunotherapy of breast carcinoma, we have synthesized ErbB2 inhibitors using 4-
thiazolidinones which represent an important class of heterocyclic compounds because of its diverse
biological activities. We herein report Propylphosphonic anhydride (T3P

)-DMSO mediated oxidation of

alcohols to carbonyl compounds and their subsequent cyclization with aryl/hetero aryl amines and
thioglycolic acid to afford 4-thiazolidinones. Synthesis of 4-thiazolidinones directly from alcohols has been
carried out for the first time. Mild reaction conditions, wide functional group tolerance, ease of workup and
good yields are the noteworthy features of this protocol. Docking studies were performed into the ErbB2
active site to determine the probable binding pattern. Antiproliferative assay results indicating that some of
the thiazolidinone derivatives own high antiproliferative activity against MCF-7. Compounds that inhibit the
kinase activity of ErbB2 after binding of its cognate ligand are of potential interest as anticancer agent
deserves future research.







Synthesis of novel benzoxazine-based aglycones that targets glycosidases and sodium/glucose
cotransporter 1

Bharathkumar H,
1
Shanmuga Sundaram M,
2
Jagadeesh Das,
3
, Shardul Paricharak,
4,5
Anusha Sebastin,
1

Babu Rajeev,
1
Srinivas V,
1
Rangappa K.S,
3
Adriaan IJzerman,
5
Kemparaju K,
2
Girish KS,
2
Andreas
Bender,
4
and Basappa
1


1
Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Palace Road,
Bangalore-560001, India;
2
Department of Studies in Biochemistry, University of Mysore, Mysore 570006,
India;
3
Department of Chemistry, University of Mysore, Manasgangotri, Mysore-560001, India;
4
Unilever
Centre for Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, CB2
1EW, Cambridge, United Kingdom, and
5
Division of Medicinal Chemistry, Leiden/Amsterdam Center for
Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Glycoside hydrolases catalyze the selective hydrolysis of glycosidic bonds in oligosaccharides,
polysaccharides, and their conjugates. -glucosidases occur in all domains of living organisms and
constitute a major group among glycoside hydrolases. On the other hand, the benzoxazinoids occur in living
system and acts as stable -glucosides namely, 2-(2,4-dihydroxy-7-methoxy-2H- 1,4-benzoxazin-3(4H)-
one)--D-gluco-pyranose. Here, we synthesized the aglycones by using the chloro acetic acid catalytic
system to the aerobic oxidative synthesis technology to develop novel heterocycles like 1,3-benzoxazines
efficiently from the one-pot reaction of aldehydes with 2-aminobenzyl alcohols. These benzoxazines
structurally mimic the naturally occurring aglycons like MBOA (6-methoxybenzo[d]oxazol-2(3H)-one,
BOA (benzo[d]oxazol-2(3H)-one). These benzoxazines [3-(2,4-dihydro-1H-benzo[d][1,3]oxazin-2-yl)-4H-
chromen-4-one (HDA-36), 4-(2,4-dihydro-1H-benzo[d][1,3]oxazin-2-yl)phenol (HDA-37), 4-(7-chloro-2,4-
dihydro-1H-benzo[d][1,3]oxazin-2-yl)phenol (HDA-38) shows inhibitory activity towards glucosidase is
significant when compared to acarbosetetrasaccharide with a IC
50
Values (g/ml) of 4.0, 3.9 and 3.5
respectively. Based on the target prediction tool (NB classifier) results these aglycones (benzoxazines)
potentially target the sodium/glucose co transporter1 with a score of 2.70. The in vitro glycosidic activity
was correlated with the in silico docking correlations with a high docking score for the HDA-38 towards the
aglycones binding site of glycosidase. In addition, the in vitro and in vivo anti-hyperglycemic effect of
HAD-38 significantly reduced the plasma glucose concentration of the mouse treated with maltose as
substrate when compared to maltose control group.








Structural Insights to Target Epidermal Growth Factor Receptors Dimerization with Novel Small-
Molecule Inhibitors
APPAJI DOKALA
Department of Pharmaceutical Chemistry, Vishnu Institute of Pharmaceutical Education and Research,
Narsapur-502313, Medak

The epidermal growth factor (EGF) receptor is a receptor tyrosine kinase involved in the control of cell
proliferation. EGF receptor dimerization is a pre-requisite for kinase activation, and is the basis for
exploring the feasibility of inhibiting EGF receptor activation by blocking dimer formation with small
molecules. A compound 32, initially identified by virtual screening, was shown experimentally to inhibit
EGF receptor kinase activation in a dose-dependent manner. This compound blocked EGF-stimulated dimer
formation as measured by chemical cross-linking and luciferase fragment complementation. This first-
generation lead compound represents the best small-molecule inhibitor of EGF receptor activation that is not
directed against the intracellular kinase domain.

















Synthesis, Molecular docking, ADMET studies and Cytotoxic screening of Some Novel Nitrogen
Bridge head Heterocycles Containing 1,2,4-Triazolo[3,4-B](1,3,4)-Thiadiazole Moiety
Bincy B.C*, Jubie.S, Naga Srinivas T, Ashish Wadhwani
1
, Patel Viral
1
and Md.Afzal Azam
Department of Pharmaceutical Chemistry
1
Department of Pharmaceutical Biotechnology, JSS College of
Pharmacy, (Off Campus-JSS University, Mysore), Udhagamandalam, India-643001

A series of novel nitrogen bridge head heterocycles containing 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole moiety
(1a-e) and (2a-e) were synthesized in successful yield, by cyclocondensation of 4-amino-5-substituted-
(1,2,4)-triazolo-3-thiol with different substituted aromatic aldehydes in presence of potassium carbonate. To
investigate their anticancer activity on the structural basis, in-silico molecular docking studies have been
carried out. All the compounds were docked towards the enzymes human fatty acid synthase thioesterase
domain [PDB ID: 2PX6] by GLIDE integrated maestro (9.3 version). The compounds 1c, 1d, 1e, 2b, 2e
showed comparable results when compared to the known human fatty acid synthase thioesterase domain
inhibitor orlistat. Also, they exhibited desirable ADMET properties. Further the compounds have screened
for their in-vitro cytotoxicity towards MCF cell lines by SRB method. It has been observed that there is a
significant correlation between in-silico and in-vitro studies.
Key words: triazolothiadiazole,cytotoxicity,in silico,human fatty acid synthase, ADMET.

















Design, Synthesis and Biological Evaluation of 6, 7-Dimethoxy-N-
Phenylquinazolin-4-Amine derivatives as Potent CLK1 Inhibitors
Digambar Kumar Waiker
a
, C. Karthikeyan
a
, Olivier Lozach
b
, Laurent Meijer
b
. Prof. Piyush Trivedi
a

School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport road Bhopal,
Madhya Pradesh-462033
Protein Phosphorylation and Human Disease Group, USR3151, Station Biologique, B.P. 74, 29682 Roscoff
Cedex, Bretagne, France

CLK1 was one of the first dual specificity kinases discovered. CDC-like kinase (CLK) is a protein kinase
with dual specificity; it can phosphorylate both serine/threonine and tyrosine residues. Quinazoline is the
most promising scaffold for drug discovery efforts targeted towards kinases. 6, 7-dimethoxy-N-
phenylquinazolin-4-amine derivatives (DW-01 to DW-10) were designed, synthesized and evaluated for
kinase inhibitory activity against five kinases implicated in neurodegeneration (CLK1, DYRK1, GSK 3 ,
CDK5, CK1). Compound DW-05 was identified as a highly potent inhibitor of the CLK1 (IC50=1.5M) and
GSK3 , (IC50=3M). Docking studies suggested that substituted 6, 7-dimethoxy-N-phenylquinazolin-4-
amine bind to the ATP-binding site of the both enzymes deriving their affinity mainly by interactions with
apolar side chains of the ATP-binding pocket as well as by formation of specific hydrogen bonds with the
amino acid residues in the hinge region of kinase.

















A newer outlook to cardiac arrhythmia: Lead development by targeting Calsequestrin and its calcium
binding
Harapriya Chakravarty,
1
Amit Kumar,
2
Naresh C. Bal,
3
Chandralata Bal,
1
Ashoke Sharon
1

1
Department of Applied Chemistry, Birla Institute of Technology, Mesra, Ranchi, Jharkhand-835215, India.
CRS4, Bioengineering group, Science and Technology Park Polaris, Piscina Manna, Italy
3
Department of
Physiology and Cell Biology, The Ohio State University,College of Medicine, Columbus, OH 43210

Cardiac dysrhythmia (which is also known as arrhythmia or irregular heartbeat) is any of a large and
heterogeneous group of conditions which is due to abnormal electrical activity in the heart and very often
has an extremely high unpredictability and noxious consequence. Arrhythmias are complex health issues
affecting many people worldwide. Research over the years has established that these conditions arise due to
altered Ca2+-handling, although exact molecular details are still under investigation. Various mutations in
calsequestrin, lead to fatal cardiac arrhythmias called Catecholaminergic polymorphic ventricular
tachycardia. In order to understand how a molecule could modulate its polymerization our first approach
was to understand its calcium binding with its polymerization. Our present work is on the determination of
the structure of calsequestrin using Prime for Homology modeling, Loop refinement followed by Molecular
dynamics simulation to envision its calcium binding properties. The molecular dynamics simulation at
various calcium concentrations showed how the C-terminal, which is missing in the crystal structure, adopts
a favorable orientation with an increase in calcium concentration. Moreover understanding of specific
calcium binding sites shows us the ways that which of these sites are more likely to buffer calcium. Since
there is no reported binding site for binding of calsequestrin modulator, we used Site map for the
determination of ligand binding sites, the possible lead molecules were docked to find a favorable
interaction with the protein inhibiting the N-terminal insertion and disrupting the polymerization.
The preliminary designed molecules were synthesized and biological studies provided significant results as
possible polymerization inhibitor. Thus, the further lead optimization and biological studies are in progress,
which could have a significant role as an anti
arrhythmic agent. (Acknowledgement:
Department of Biotechnology, Government of
India for Financial Support)

Fig1-Synthesized molecule interacting at the
interface of two chains










Structure guided designing of potential lead motifs against Cancer

Arun Kumar V.A
1
, Keshav Mohan
2

1
Department of S & H (Computer Applications), Sathyabama University, Chennai. India
2
SVN College f Engineering, Mavelikkara, Kerala , India. Corresponding Author
1

E-mail:akva1234@yahoo.com

On the basis of stereo specific information obtained from the crystal structures of CDK2, indole and
chromene analogues were designed by suitably substituting the pharmacophores on their moiety and docked
with target protein for calculating binding affinities. The binding affinities were represented in glide score.
(5E)-5-[(1-methyl-1H-indol-3-yl)methylidene]-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I
1
), (5E)-5-(1H-
indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I
2
) and 2-amino-4-(4-methyl phenyl)-5-
oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C
9
)were selected for synthesis and biological testing
based on vital interactions. Compounds I
2
and C
9
were proved to be active against MCF-7 and HeLa cell
lines.
Keywords: CDK, pharmacophores, MCF-7, HeLa.















Identification of Potential Inhibitors for Regulating Keap1-Nrf2 Function

Prashant Deshmukh, Lata Chaunsali, Manjula Ramu and Balasundaram Padmanabhan
Department of Biophysics, National Institute of Mental Health and Neuroscience, Bangalore 560 029, India.

Neurodegeneration in humans is known to occur as a result of several primary causes, including expression
of certain gene alleles, toxicant administration, and aging. Oxidative damage/stress (OS) has been associated
with various neurodegenerative diseases (ND) including Parkinsons disease, amyotrophic lateral sclerosis
(ALS), and Alzheimers disease, as well as non-neurodegenerative conditions such as cancer and heart.
Clinical trials are being conducted to establish the potential of antioxidant therapeutics; however, to date, no
drugs are available in the market.
The activation of Nrf2/ARE in the Phase II defence system regulates the expression of antioxidant
enzymes. Under unstressed conditions, Nrf2 binds to Kelch-like ECH-associated protein 1 (Keap1) and
undergoes constitutive proteasome-dependent degradation. In the presence of OS, Keap1 changes its
conformation and releases Nrf2, which translocate into the nucleus and binds to ARE; thereby activate
several cytoprotective genes. The expression and/or activation of Nrf2 in neurons can be strongly protective,
and thus the Nrf2 system is a potential drug target in neurodegenerative diseases.
In this context, we have been working on the Keap1-Nrf2 system to discover potential inhibitor
compounds for Nrf2 activation, by rational drug discovery approach. We present here new hits of Keap1
inhibitors, obtained by in-silico method, and confirmed by preliminary fluorescent-based binding studies.












Structure based docking assisted identification of 4-(benzylidene)hydrazinothazoles as novel aurora
kinase inhibitors
Sarah T., Sreejalekshmi K. G
*
Department of Chemistry, Indian Institute of Space Science and Technology, Thiruvananthapuram, Kerala,
695 547, India
E-mail:Sarah.11@iist.ac.in

Anti-cancer drug development, despite the huge investment and extensive research, is yet to
conquer many challenges including selective targeting and high specificity of drugs. The availability of huge
number of potential lead molecules as well as targets for anti-cancer drug development make the discovery
and development process further more complex where the right combination of activity, specificity, stability
and safety studies on a selected candidate is a long term and expensive research. With the advent of
powerful and accurate computational tools, researchers currently exploit molecular docking to predict the
ligand-target site interactions which ultimately take a leading role in identifying candidate targets for anti-
cancer therapy as well as assist in the discovery and optimization of novel anti-cancer agents.

Aurora kinases, one of the key regulators of mitosis, frequently over expressed in human
cancers are among recently identified targets for anti-cancer agents. Aberrant expression of these kinases
leads to chromosomal instability and derangement of multiple tumor suppressor and onco-protein regulated
pathways. Preclinical studies and phase I and II clinical trials of multiple aurora kinase inhibitors as targeted
anticancer drugs, most of them belonging to the family of heterocycles, have also provided encouraging
results.

Our longstanding interest in the design of synthetic routes to pharmaceutically relevant
heterocyclic systems, their chemical synthesis and biological evaluation have identified aminothiazole
derivatives as potential anti-cancer agents. Currently our research focus is on 4-hydrazinothiazole
derivatives. In the present work, virtual screening and molecular docking of novel 4-
(benzylidenehydrazino)thiazole derivatives as aurora kinase inhibitors and the biological evaluation of their
potential as anticancer agents is discussed.























Combination therapy of 3, 3-Diindolylmethane and 5-Fluorouracil enhances anticancer activity in
human cervical cancer (HeLa) cell line by inducing apoptosis.
V.L.Maruthanila and S.Mirunalini*
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University,
Annamalainagar 608 002, Tamilnadu, India
E.mail: mirunasankar@ gmail.com.

Combination therapy is the most effective treatment strategy in cancer to overcome drug toxicity and drug
induced resistance. The preliminary aim of the present study was to investigate the combined treatment of 3,
3-diindolylmethane (DIM) and 5-fluorouracil (5-FU) against human cervical cancer (HeLa) cell line. The
HeLa cancer cells were treated with varying concentrations of DIM and 5-FU. Cytotoxicity of experimental
drugs was tested using MTT assay to find IC
50
value. Isobolographic method was used to calculate
combination index (CI) values from cell viability data. More over the apoptotic morphological changes have
been measured by AO-EtBr staining and DNA fragmentation CI analysis, respectively. Both DIM and 5-FU
exhibited time and concentration dependent inhibition of HeLa cell proliferation. In cytotoxicity assay the
concentration in which 50% of cell death (IC
50
value) for DIM, 5-FU and in combination of DIM with 5-FU
respectively and hence for further experiment we were chosen these concentrations. Apoptotic
morphological changes and DNA damage were observed more in DIM with 5-FU (combination therapy)
when compared to individual treatment. More over the CI value was found to be (0.36) suggested that more
synergistic effect of DIM and 5-FU against HeLa cells. Our result suggest that DIM in combination with 5-
FU could overcome the drawback of 5-FU therapy while capitalizing on the positive effects of this proven
therapy. Hence developing DIM and 5-FU a potential combinational therapy against various types of
malignancy will be promising in the future.
Keywords: HeLa cell line, DIM, 5-fluorouracil, apoptosis, cytotoxicity, combination therapy.









Molecular Modeling and functional site prediction of HSP70 protein: Japanese
Encephalitis disease
Shivani Pandey
1
, Anshul Tiwari
1,2
, Prachi Srivastava
1

1 AMITY Institute of Biotechnology, AMITY University Uttar Pradesh, Lucknow, UP, India
2 Dept. of Ophthalmology, King Georges Medical University, Lucknow, UP, India

Abstract
Japanese Encephalitis (JE) is a mosquito borne viral disease caused by JE virus. It is manifested by seizure,
usually begins with sudden onset of fever, headache, vomiting, change in mental status, focal neurologic
deficits, generalized weakness and movement disorder over the next few days. The treatment of Japanese
Encephalitis infection is carried out with neutralizing monoclonal antibody against the E protein which did
not inhibit the virus from binding to the cell surfaces, but strongly inhibits Japanese Encephalitis virus-
induced cell fusion and internalization of the virus into the host cells. 'Heat shock protein 70' (Hsp70) was
identified as a putative receptor for JEV. Recruitment of HSP70 into lipid rafts is required for activation of
the phosphoinositide 3-kinase/Akt signalling pathway in the early stage of JEV infection. ;hus, /SPC0 plays
a maLor role in progression o7 disease. Protein 3D structures are functionally very important and play a
significant role disease progress; hence this 3D structure is better target for further drug designing and
relative studies. We developed 3D model structure of /SPC0 protein involved in Japanese encephalitis.
Functional site prediction is a very important and related step; hence, in the current course of analysis, we
predicted putative functional site residues in the target protein. Molecular model of the protein of Japanese
encephalitis disease as documented in this study may helpful in understanding structural insights, and may
lead to the establishments of prophylactic and therapeutic approaches for the same.
Key Words: Japanese encephalitis virus, Molecular Modeling, HSP70








Molecular Dynamics
Simulation
& Quantum Mechanics
















Scrutinise of Single Nucleotide Polymorphism (SNPs) in Human Dihydro Orotate
Dehydrogenase (DHODH) through In silico and to Ascertain Structural
Importance

Sureka. K
1
, Kalaiarasan. P
2
and Jeyakanthan. J
*

Structural Biology and Biocomputing Lab
1
Department of Bioinformatics, Alagappa University, Karaikudi - 630 003, Tamil Nadu, India.
* Email: LLkanthan@gmail.com
2
National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi -
110067


Pyrimidines have numerous imperative functions in cellular physiology, as they are used in
the formation of DNA, RNA, phospholipids, and pyrimidine sugars. The purD gene encodes Dihydro
Orotate Dehydrogenase (DHODH) and it is a key enzyme in nucleotide synthesis. It catalyzes the
fourth committed step in the de novo pyrimidine biosynthesis pathway. SNPs associated with
complex disorders can cause, destroy or alter protein coding sites. Single amino acids switches in the
purD gene are the genetic variations that account for assorted forms of cancer. To the best of our
acquaintance, until now there is no study on the purD gene. Therefore, this study was undertaken to
find the functional nsSNPs in purD. To accomplish this goal, data existing in the dbSNP database
and different computer programs can be used. Using in si(ico methods, we examined the genetic
variations that can alter the expression and function of the purD gene. Using a sequence homology-
based Sorting Intolerant from Tolerant (SIFT) server for analyse the non synonyms, structure-based
method via PolyPhen server indicated that percentage of non-synonymous polymorphism may
modify protein function and structure. Pupa Suite software showed that the SNPs will have a
phenotypic consequence on the structure and function of the altered protein. Structure analysis was
performed on the key mutations that occur in the native protein coded by the purD gene that causes
transplant rejection, rheumatoid arthritis, psoriasis. Gromacs software was used to perform energy
minimization and molecular dynamics simulations of the DHODH protein before and after mutation.
Furthermore, in the native and altered protein models (mutated residues) amino acid residues were
determined and secondary structures were observed for solvent accessibility to confirm the protein
stability. The functional study will guide us for further studies in this investigation.

Keywords: SNPs, Modelling, Molecular dynamic simulations, Pyrimidine biosynthesis


MD-Simulation and Docking studies of hIMPDH-IMP analog complexes: A Step
towards the Design of Antileukaemic Agents.

Deepak K. Mishra
1
, Bishnu P. Mukhopadhyay1
*
, Soumita Mukherjee
1


1. Department of Chemistry, National Institute of Technology-Durgapur-713209, India

Inosine Monophosphate Dehydrogenase (IMPDH) plays very important role in Guanosine
Monophosphate (GMP) biosynthesis. Type I hIMPDH is expressed at lower levels in all cells,
whereas type II is especially observed in acute myelogenous leukaemia, chronic myelogenous
leukaemia cancer cells, so it is thought to be an active target for leukemic drug design. Based on
binding affinity of IMP (in presence of NAD
+
) in the catalytic pocket (having Cys 331) of
hIMPDH-II and considering the geometrical/electronic consequences of interaction of IMP with
the Arg 322, Asp 274, Asp 364, Asn 303 and Ser 68 in the different X-ray and simulated
structures, we have modified/modelled a few number of IMP derivatives which can interact
effectively in this mono-nucleotide binding region. Optimization of ligand structure, followed by
docking in enzyme, solvation, energy minimization, of the Protein-Ligand complexes and their
successive all atoms MD-
Simulation studies (by VMD program plugin with NAMD) have been made up to 25 ns. After
critical investigation of different snapshots, the stereochemical quality, binding affinity/energy
(Ligand-Receptor Van der Waals, Electrostatic, Hydrogen Bond, Solvation Free Energies and
Conformational Entropy) of each modified ligand is calculated (by PEARLS server) etc. of the
ligand within the enzyme complex have been checked and we have screened two IMP-analog
structures (Fig. 1) which may think to act as better inhibitor for IMPDH-II isoform. The drug
likeness and drug score of the modelled compounds are observed to be better.
DA9// +11. Page .7+

Designed isomorphism: A combined experimental and molecular simulation
study

Dinesh Kumar
a
, Rajesh Thipparaboina
a
, Nalini Shastri
a, *
a
National Institute of Pharmaceutical Education & Research, Hyderabad, India
E-mail: nalini@niperhyd.ac.in, dinesh.niperOM@gmail.com


In this study we designed the isomorphs/crystal habits of nifedipine (Nif) followed by the
correlations between the experimental crystal habits and simulated morphologies.
Material studio 6.1 of Accelrys was used for molecular mechanics (MM) and molecular
dynamics (MD) studies.

Modified habits with iso-diametric morphology were observed in following solvent and solvent:
anti-solvent pairs: chloroform: hexane, chloroform: iso-propyl alcohol (IPA), dichloromethane
(DCM), DCM: IPA, and ethanol: hexane. Presence of any solvates/polymorphs was ruled out by
using DSC, TGA, FTIR and p-XRD. A solvent effect was introduced by surface docking to
bridge the gap between experimental & simulated habits as they deviated from BFDH,
morphology growth and equilibrium morphology. MD was performed and modified attachment
energy was calculated to get final morphology.

The achieved predictions were found to be in good agreement with experimental habits
(statistically significant with p<0.05). Similarly, significant enhancement (1.5-2.5 times) in
solubility and dissolution behaviour of modified habits was also observed. Nif with chloroform:
IPA combination showed iso-diametric habit with better solubility and dissolution rate attributed
to their high surface/volume ratio. Good correlation was observed between polarity of
crystallization solvents and nature of functional moiety of specific facet. This methodology could
approve as a powerful tool for selection of habit modifying solvents in other crystallization
systems as prediction of crystal habits was demonstrated successfully.



References:
Yani, Y.; Chow, P. S.; Tan, R. B. H. Mol. Pharm. 2011, 8, 5, 1910-1918.
Yang, W.; de Villiers, M. M. Euro. J. Pharm. Biopharm. 2004, 58, 3, 629-636.
Schmidt, C.; Ulrich, J. Chem. Eng. Technol. 2012, 35, 6, 1009-1012.
Chen, J.; Trout, B. L. Cryst. Growth Des. 2010, 10, 10, 4379-4388.



DA9// +11. Page .7.


In-vitro meets in-silico: Ligand discrimination by TPR motif in Toc64 from Arabidopsis thaliana

Rashmi Panigrahi
1
, Abdul Adina-Zada
2
, Jim Whelan
3
and Alice Vrielink
1
1,2
School of Chemistry and Biochemistry, University of Western Australia, Perth-6009
3
Plant energy biology, ARC centre of excellence, University of Western Australia, Perth-6009


Protein translocation across the membrane, aided by specific receptors, is an ubiquitous and essential
process in every cell. The receptors involved in protein translocation can be classified into two categories:
1) those that recognize precursor proteins through interaction with their specific pre-sequences and 2)
those that recognize cytosolic transporters (chaperones) which are involved in the delivery of precursor
proteins to the import machinery for the specific organelle to which they are targeted [1,2]. In the latter
case, often the Tetratricopeptide repeat (TPR) motifs are present in receptor and have been shown to aid
in the recognition of the precursor protein pre-sequence. The TPR motif therefore, plays an important
function in its ability to form protein-protein interactions.
The Translocon outer membrane chloroplast 64kDa (Toc64) protein is a component of Toc core protein
complex in Arabidopsis thaliana [3]. It has a C-terminal 3-TPR domain, which might recognize the
conserved C-terminus of the chaperone proteins, Hsp70 and Hsp90. In the present study, we focus on the
selectivity of C-term Hsp70 and C-term Hsp90 recognition by atToc64. Here we have quantitatively
assessed the contribution of TPR-mediated peptide recognition to complex formation using Isothermal
Titration Calorimetry and alanine scanning experiments. We have carried out in-silico simulation studies,
combined with essential dynamics to understand the detailed interaction profile and dynamics assoicated.
Guided by the above methods, we are able to identify the important residues in the ligands that mediate
interaction.



DA9// +11. Page .7*

Carbon based nanostructures as multifunctional platforms for pyrazinamide drug loading
and delivery onto pncA protein - a molecular dynamics study
Nabanita Saikia and Ramesh C. Deka
*
Department of Chemical Sciences, Tezpur University,
Napaam, Tezpur784 028, Assam, India
E-mail: ramesh@te2u.ernet.in, nste2@te2u.ernet.in

Nanomaterials such as carbon nanotubes (CNTs) and graphene with carbon constituting the
fundamental building block element has attracted tremendous potential interest in a wide range
of applications driven by its unique structure and exceptional electronic, mechanical, thermal and
optical properties. The present study investigates the role of CNTs and graphene in the delivery
of PZA antitubercular chemotherapeutic onto the active binding site of pncA protein using
molecular dynamics (MD) simulations. PZA drug in presence of nano support exhibits
specificity towards interaction with pncA. The interaction of graphene with pncA residues is
more flexible compared to CNTs rendered from the open surface framework, with the graphene
sheet penetrating into the binding pocket of pncA, whereas in case of CNTs due to its stable
framework it prefers to orient around the binding pocket of pncA. The study underlines that the
presence of nanocarrier does not affect the protein conformation and assists in enhanced PZA
binding with the amino acid residues of pncA, thereby achieving the target specific drug delivery
module helpful in frontline tuberculosis chemotherapy.
References:
N. Saikia, A. N. Jha and R. C. Deka, RSC Adv., 2013, DOI: 10.1039/C3RA42534G.
N. Saikia, A. N. Jha and R. C. Deka (communicated).
N. Saikia, S. Rajkhowa and R. C. Deka, J. Comput. Aided. Mol. Des. 2013, 27, 257276.

DA9// +11. Page .74


In silico Screening, Activity and Molecular Dynamics Simulation studies of nsSNPs in
Pyruvate Kinase M2

Ponnusamy Kalaiarasan
1
, SubaraoNaidu
2
, Rameshwar NK Bamezai
1
1
National Centre of Applied Human Gentics, School of Life Sciences, Jawaharlal Nehru
University, New Delhi
2
School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi


Functional role of 2 known mutations and 29 non-synonymous polymorphisms (nsSNPs) of
Human Pyruvate Kinase (PK) M2 was investigated by in silico and in-vitro functional studies.
Prediction of deleterious substitutions based on sequence homology & structure based servers,
SIFT, PANTHER, SNPs & GO, PhD-SNP, SNAP and PolyPhen, depicted 19% common
between all the mentioned programmes. SNPeffect and HOPE together showed three
substitutions (C31F, Q310P and S437Y) in silico as deleterious and functionally important. To
characterize these further, in-vitro activity assays of the wild and variant human-PKM2 proteins
were carried out, which showed C31F and S437Y variants of PKM2 with reduced activity, while
Q310P variant was catalytically inactive. The compromised allosteric nature of S437Y nsSNP
was observed to be due to the absence of the effect of allosteric activator, Fructose 1-6
bisphosphate (FBP), and binding. This was corroborated through molecular dynamics (MD)
simulation study, as carried out for other variations as well. We propose that these functionally
important variations in PKM2 gene could have a bearing on cancer metabolism, since PKM2 has
been implicated in cancer in the recent past.

Keywords: nsSNPs, Pyruvate Kinase M2, Enzyme Assays, Molecular Dynamics Simulations.


DA9// +11. Page .70


Molecular dynamics and ?inding studies of 5oumarin *erivatives wit( !uman
serum al)umin and its )iological significance3

*aniel Heggoni
.
8 ; Ma(es(
0
8 *3M3Manid(ar

8 5(andra mouli
.$
8 '3,a7agopal
.
3
*epartment of 2lant 'cience
.
8*epartment of ?ioc(emistry
0
'c(ool of =ifesciences
.80
8 -niversity of
!ydera)ad
.80

*epartment of 5(emistry8 'ri venkates(wara university3

oumarins o9e their class name to _coumarou= the ,ernacular name o7 tonka 8ean.
5*ipteryx odarata 9illd,Fa8aceae6, %any coumarins and their deri,ati,es exert, anti
tumor,anti,iral,anticoagulate,anti3in7lammatory and anti oxidant e77ect as 9ell as anti micro8ial and
en2yme inhi8ition properties./ere, 9e studied the 8inding o7 synthesi2ed coumarin deri,ati,es 9ith
human serum al8umin 5/S"6 at physiological p/ C.2 8y using 7luorescence spectroscopy, circular
dichroism spectroscopy, molecular docking and molecular dynamics studies. By addition o7 coumarin
deri,ati,es to /S" the maximum 7luorescence intensity 9as reduced due to :uenching o7 intrinsic
7luorescence upon 8inding o7 coumarin deri,ati,es to /S". ;he 8inding constant and 7ree energy 9ere
7ound to 8e 4.M`?0
4
%
3?
, 3M.'4 (cal %
3?
7or $?! ?.'`?0
4
%
3?
, 3P.PO (cal %
3?
7or $2, and C.&`?0
4
%
3?
, 3
M.MP (cal %
3?
7or $4. ;he * spectroscopy sho9ed that the protein secondary structure 9as partially
un7olded upon 8inding o7 coumarin deri,ati,es. Further, the molecular docking studies sho9ed that
coumarin deri,ati,es 9ere 8inding to /S" at su83domain ..",.",..." and ...B 9ith the hydropho8ic
interactions and also 9ith hydrogen 8ond interactions. "dditionally, the molecular dynamics studies
contri8uted in understanding the sta8ility o7 protein3drug complex system in the a:ueous solution and
the con7ormational changes in /S" upon 8inding o7 coumarin deri,ati,es. (no9ing the precise
conditions 9ill greatly help in the study o7 drug distri8ution, deli,ery and interactions play a maLor in
de,elopment o7 coumarin deri,ati,es inspired drugs.

DA9// +11. Page .73


/M, and Molecular modelling studies of peptide conformations

;i7o ;eorge8 'ud(ir ?a)u8 '3 ,ag(ot(ama
$%# #esearch entre, .ndian .nstitute o7 science, Bangalore3PM00?2, .ndia.

Ie ha,e undertaken t9o di77erent studies, 9here $%# and molecular modelling is used to understand
certain peptide con7ormations. ;he 7irst is on amyloid 7ragment called "3?2 9hich is $3terminal ?2
residue 7ragment *3"3E3F3#3/3*3S3@3T3E3) o7 "342. .n this study 9e ha,e sho9n "luminium metal
interaction 9ith the peptide 9hich may 8e responsi8le 7or aggregation e77ect. $%# analysis pro,ided
the solution structure o7 this amyloid 7ragment. Further metal titration 9ith peptide indicated possi8le
interaction site. Iith Schrodinger so7t9are molecular modelling 9as carried out to ascertain the
8inding site in the 7ollo9ing manner: $%#3deri,ed structure 9as exported to macro3model module o7
the so7t9are. Potential aluminium 8inding site 9ere identi7ied near the charged residues such as "sp
and @lu 9hich sho9ed distinct chemical shi7t changes in $%# titrations. ;hey turned out to 8e 9ell
suited 7or metal coordination through their car8oxylate groups. "luminium metal atom 9as placed in
such positions and 9hole 8ound structure 9as restrained energy minimi2ed in ,acuum. >P<S 200P 7orce
7ield and Polak #i8iere onLugate @radient 5P#@6 method 7or energy minimi2ation 9as used. >ut o7
t9o potential sites, the lo9er energy site 9as recogni2ed as the proper 8inding site as it agreed 9ith
8etter coordination and concurred 9ith $%# chemical shi7t changes.

;he second proLect that 9e ha,e undertaken is molecular dynamics studies on Lcis B transM
isomerisation o7 proline containing short peptides. Ie consider here three peptides 9ith the general
se:uence Pi,3
*
Pro3Hxx3
<
<eu3$/%e 9here Hxx S
<
Pro,

Pro,
/
Pro 5

Pro S <32,23dimethyl3?,'3thia2olidine3
43car8oxylic acid, and
/
Pro S <3,23methyl3?,'3thia2olidine343car8oxylic acid6. ;hough they all 7orm 3
turns, they undergo cis D trans isomerisation under di77erent conditions. Some o7 the peptide sho9 only
cis 7orm in H3ray crystal structure, 8ut in solution they undergo exchange 8et9een cis and trans 7orms as
they sho9 t9o distinct 7orm 8y dou8ling o7 all $%# resonances. ;he ratio o7 these 7orms also ,aries
8et9een peptides. Solid state $%# o7 one o7 the peptides again yielded dou8le con7ormers coexisting,
7or 9hich H3ray structure could not 8e o8tained. ;he solution $%# o7 the same sho9ed only one 7orm.
;o understand these inter3con,ersions, 9e took up molecular dynamic studies o7 all three peptides
using ,arious methods and the results 9ould 8e presented.


DA9// +11. Page .77

Importance of Water Molecules in Determining the Biological Activity of Ligands: A Case
Study of Interleukin-1 Receptor Associated Kinase (IRAK-4) Inhibitors
%alkeet Singh Bahia and >m Silakari-
%olecular %odeling <a8 5%%<6, *epartment o7 pharmaceutical Sciences and *rug #esearch, PunLa8i
0ni,ersity, Patiala, ?4C002
-orresponding author E3mail: omsilakari@redi77mail.com

.nnate immune system pro,ides an immediate de7ense against the in,ading pathogens and
su8se:uently ser,es as an essential component o7 host=s natural 7irst line de7ense. ;his system is
composed o7 se,eral mononuclear cells, especially macrophages, 9hich encounter the pathogens either
upon tissue contact or in the systemic circulation upon in,asion o7 pathogen into the 8loodstream.
;hese cells mount immune response through signals mediated 8y their trans3mem8rane toll like
receptors 5;<#s6 and interleukin3? receptors 5.<3?#s6 resulting in the secretion o7 pro3in7lammatory
cytokines. ;he molecular understanding o7 these signaling path9ays lead to disco,ery o7 an
indispensi8le element, i.e. .#"(34, 9hich is crucial 7or mediating the do9nstream cellular signaling o7 .<3
?#s, .<3?O# and a num8er o7 ;<#s. ;he acti,ation o7 these receptors triggers se,eral do9nstream
proteins that ultimately results in the expression o7 %"P( and $F3NB mediated in7lammatory responses.
;hus, the modulation o7 .#"(34 kinase acti,ity 9ould 8e an attracti,e therapeutic strategy 7or the
treatment o7 ,arious in7lammatory and immune related conditions in the 7uture.
@enerally, 7or the docking analysis, most o7 the medicinal chemists do not consider the 9ater molecules
due to their complexity during docking, ho9e,er sometimes they may 8e essential in determining the
signi7icant interactions and orientations o7 the ligands molecules into the acti,e sites o7 proteins. Iater
molecules may either ser,e to 7ill the ca,ity or to 8ridge the ligand molecule 9ith acti,e site amino acid
residues o7 the protein. ;hus, the remo,al o7 9ater molecules, 8lindly, may signi7icantly a77ect the
outcomes o7 docking experiments. .n the light o7 a8o,e present study 9as aimed to determine the
importance o7 9ater molecules 7or the inhi8itors o7 .#"(34 using molecular dynamic 5%*6 sal,ation and
docking simulations.
.nitially, protein 9as sol,ated 9ith ;.P'P 9ater molecules 7or 2 ns using *esmond molecular dynamics
program, and the resulting 7rames o7 the proteins 9ere clustered. "7ter clustering, '0 7rames 9ere
selected 7or analysis, and those 9ater molecules 7orming interactions 9ith the acti,e site amino acid
residues 9ere selected. ;herea7ter, the energy o7 each 9ater molecule 9as calculated, and those ha,ing
high energy contri8ution as 9ell as conser,ed in each 7rame 9ere selected 7or the docking analysis. ;his,
analysis success7ully helped to analy2e the structural 9ater molecules 9hich determine the interactions
and orientations o7 the inhi8itor molecules 9ithin the acti,e site o7 .#"(34 and conse:uently can 8e
used 7or the designing o7 potent and selecti,e inhi8itors o7 .#"(34.





DA9// +11. Page .7E

Probing the Conformational Flexibility of Monomeric FtsZ in GTP-Bound, GDP-
Bound, and Nucleotide-Free States
Kathiresan Natarajan
Jawaharlal Nehru Center for Research - Bangalore
1)stract:
;he mechanism o7 nucleotide3regulated assem8ly and disassem8ly o7 the
prokaryotic cell di,ision protein FtsE is not yet clearly understood. .n this 9ork, 9e
attempt to characteri2e the 7unctional motions in monomeric FtsE through
molecular dynamics simulations and essential dynamics 5E*6 analyses and
correlate those motions to FtsE assem8ly and disassem8ly. #esults suggest that
the nucleotide 8inding su8domain o7 FtsE can s9itch 8et9een multitudes o7
cur,ed con7ormations in all nucleotide states, 8ut it pre7ers to 8e in an assem8ly
competent less cur,ed con7ormation in the @;P38ound state. Further, the @*P to
@;P exchange in,okes a su8tle con7ormational change in the nucleotide 8inding
pocket that tends to align the top portion o7 core helix /C along the longitudinal
axis o7 the protein. E* analyses suggest that the longitudinal mo,ements o7 /C
and the adLacent /MG/C region modulate the motions o7 3domain elements
coherently. ;hese longitudinal mo,ements o7 7unctionally rele,ant /C, /MG/C, ;',
;C, and /?0 regions are likely to 7acilitate the assem8ly o7 @;P3FtsE into straight
7ilament. >n the other hand, the o8ser,ed radial or random mo,ements o7 FtsE
residues in the @*P state might not allo9 the monomers to assem8le as
e77iciently as @;P38ound monomers and could produce cur,ed 7ilaments. >ur
results correlate ,ery 9ell 9ith recent mutagenesis data that in7erred FtsE
con7ormational 7lexi8ility and the in,ol,ement o7 the /MG/C region in assem8ly.





DA9// +11. Page .E1

A novel role for magnesium in pyrophosphate release and evidence for a
two-metal reaction in N-acetylglucosamine-1-phosphate Uridyltransferase
(GlmU)

Pravin Kumar, Ankush Jagtap
1
, Sunil Kumar Verma
1
, Neha Vithani
1
, Vaibhav Singh Bais
1
,
Ravi Tripathi
2
, Nisanth N. Nair
2
, Vijay Soni
3
, Vinay Kumar Nandicoori
3
and Balaji
Prakash
1
*

1
Department of Biological Sciences and Bioengineering, Indian Institute of Technology,
Kanpur 208016, India
2
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India
3
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi110067, India


GlmU an essential prokaryotic enzyme utilizes UTP and GlcNAc-1-P as substrates and
synthesizes UDP-GlcNAc. UDP-GlcNAc being an important precursor for cell wall synthesis
in many microorganisms, GlmU is a potential drug target. In a recent work, we have
deciphered how GlmU utilizes a two-metal mechanism to catalyze uridyltransfer reaction
(Jagtap, P. K. et al., J Mol Biol 2013). Following this, we determined three different crystal
structures of GlmU immediately following product formation. Unusually, in each structure
we observe both the products (UDP-GlcNAc and PPi) and two metal ions (Mg
2+
A
and Mg
2+
B
)
at the active site. These structures however showed distinctly different positions occupied by
PPi, depicting its movement. A comparison of these structural snapshots shows that
pyrophosphate (PPi) moves away from the active site along with one of the magnesium ions,
Mg
2+
B
that participates in catalysis. A detailed analysis of these structures shows that Mg
2+
B

while moving as a complex with PPi undergoes distinct changes in its coordination geometry
to facilitate PPi exit. Accelerated molecular dynamics simulations employed to understand
these events at molecular detail, support the view that PPi exits the active site in complex
with Mg
2+
B
. Also, the changing coordination states as observed in the crystallographic
snapshots were observed in the MD simulations that showed varying stability. Taken
together, this work presents a possible mechanism by which Mg
2+
ion would drive
pyrophosphate exit.





DA9// +11. Page .E1


Structural and Functional analysis of HEPN protein (TTHA0427) from
Thermus thermophilus HB8 - An Computational approach
Prabhu. D
1
, Surekha. K
1
and Jeyakanthan. J
1*
1
Structural Biology and Bio-Computing, Department of Bioinformatics, Alagappa University, Karaikudi-630 004.
E-Mail: LLkanthan@gmail.com

Thermus thermophilus HB8 is a gram negative aerobic bacterium, isolated in a thermal vent
from Japan in 1971 and it grows in the temperature ranges from 50 to 82C. Currently, Thermus
thermophilus HB8 genome reveals the existence of approximately 40% hypothetical proteins, from which
TTHA0427 was selected for the study. By the use of bioinformatics tools, TTHA0427 protein sequence
was predicted as HEPN protein. The HEPN protein was modeled using 1UHB as the template in
Schrodinger-Prime Module. Simulation studies of modeled Proteins were carried for 20ns and the stable
structure was identified, which is used in further docking studies and Screening of potential lead
molecules were carried out using large public library (Asinex, BindingDB, ChembridgeDB, Toslab, Zinc,
and Maybridge database), that could inhibit the HEPN protein. One top scoring compound from six
databases against HEPN protein in Virtual screening were considered for protein-ligand complex based
on Glide score. Molecular dynamics simulation study for selected protein-ligand complex for HEPN
protein was done at 10ns. The lead molecules from Binding database shows maximum stability. This
property can be harnessed in drug designing as both chemical and physical stability of protein-ligand
complex is required for its functionality.
Keywords: HEPN, TTHA0427, Antibiotic Resistance






DA9// +11. Page .E+


In - silico studies of PH0702 From Translation Initiation Factor In
Pyrococcus horikoshii OT3
J. Prajisha, R. Naga soundarya, J., Shankar Prasad Kanaujia and J.Jeyakanthan*
Structural Biology and Bio-Computing Lab, Department of Bioinformatics, Science Block,
Alagappa University, Karaikudi - 630 004, Tamil Nadu, India.
Department of Biotechnology, Indian Institute of Technology, Guwahati - 781 039, Assam, India.
Email: jjkanthan@gmail.com

Protein Translation is the crucial step in protein synthesis, involves mainly three steps namely
initiation, elongation and termination. In prokaryotes, initiation of protein translation is facilitated by the
presence of Shine Dalgarno (SD) sequence. This study focus, prokaryotic translation initiation factors.
For that, planned to work on hyperthermophilic archaeal prokaryotic organism Pyrococcus horikoshii
OT3. Control of Eukaryotic initiation factor (eiF2) is important in certain neurological processes, the
defect in eIFs or in their control can give rise to number of diseases. Thus, this study is to understand the
mechanism of translation initiation factor. The fundamental steps in translation initiation are the binding
of initiator methionine tRNA (Met-tRNA) to a small ribosomal subunit and positioning of them on the
start codon of mRNA. Translation initiation factor 2B plays vital role in delivering Met - tRNA to small
ribosomal subunit as a ternary complex with GTP and facilitating start site selection through hydrolysis of
GTP when the codon - anticodon base pairing between Met - tRNA the start codon is formed. PH0702
protein of Pyrococcus horikoshii OT3 related to translation initiation factor 2B beta subunit family. In-
silico studies were performed to model PHO702 and also verified in SAVES server, then Molecular
dynamic studies has performed to validate the stability of the protein. Modeled protein were docked with
Zn, GTP, Met tRNA were docked together using the HADDOCK online server. 30s ribosomal subunit of
Pyrococcus horikoshii OT3 were modeled. Further studies were in process
Keywords: Pyrococcus horikoshii OT3 PHO702, Protein Translation, Saves, HADDOCK





DA9// +11. Page .E.



Allosteric regulation of pro-apoptotic serine protease HtrA2: a novel mechanism presenting
prospective therapeutic strategies

Raja Reddy Kuppili, Pruthviraj B, Kakoli Bose
Integrated Biophysics and Structural Biology Lab, ACT!C, Kharghar, "avi #u$bai
e%$ail& rajaskingdo$'()g$ail*co$

+trA', a tri$eric proapoptotic serine protease plays pivotal role in $aintaining cellular
ho$eostasis by $ediating apoptosis via $ultiple path,ays* -i..erential e/pression o. +trA'
has been associated ,ith neurodegenerative diseases, hepatocellular carcino$a as ,ell as
cancers such as, ovarian, breast and prostatic thus $aking it an i$portant therapeutic target* It
has a co$ple/ tri$eric structure ,ith $ultiple do$ains that ,ork in unison to $ediate its
biological .unctions* 0pon substrate binding, the C%ter$inal P-1 do$ain in this protein
regulates its .unctions through coordinated con.or$ational changes the $echanis$ o. ,hich is
yet to be elucidated* Although allostery has been .ound in so$e o. its ho$ologs, it has not been
characteri2ed in +trA' so .ar* The $issing loops, linkers and inter.ace regions in the crystal
structure do not reveal the con.or$ational plasticity and inter%subunit crosstalk that govern
+trA' activity and .unctions* 3ur in silico studies led to prediction o. the putative binding
pocket or selective binding pocket 4SBP5 ,hich together ,ith $odeling, $olecular dyna$ics
si$ulation, en2y$ology and other bioche$ical studies helped us identi.y and de$onstrate its
role in allosteric regulation o. +trA' activity* 3ur studies hence identi.ied a novel non%
canonical binding pocket in +trA' ,hich initiates signal propagation to the distal active site
through a co$ple/ allosteric $echanis$* This non%classical binding pocket is uni6ue a$ong
+trA .a$ily proteins and thus un.olds a novel $echanis$ o. regulation o. +trA' activity and
hence apoptosis* Allosteric $odulators have been .ound to e/hibit several advantages over
conventional orthosteric $olecules such as lo, to/icity and higher subtype speci.icity*
There.ore designing suitable SBP binding peptides or peptido$i$etics $ight be an e/cellent
approach to $odulate +trA' .unctions .or devising therapeutic strategies against cancer and
other diseases it is associated ,ith*

Keywords& proapoptotic, +trA', allostery, substrate binding pocket, P-1, serine protease
do$ain
DA9// +11. Page .E*

Insights on P-glycoprotein Substrate Binding: Molecular Dynamics Simulations and In vitro
Validation
Rohit Bansal, Rameshwar Prajapati, Abhay T. Sangamwar*
Department of Pharmacoinformatics
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research
(NIPER),
Sector-67, S. A. S. Nagar, Punjab, India
Email: abhays@niper.ac.in

Abstract:
The human multidrug transporter P-glycoprotein (P-gp) contributes to the poor bioavailability of many
anticancer agents and resistance due to their over-expression in cancerous cells. For rational design of
anticancer agents which can evade P-gp specificity, a clear understanding of its substrate selectivity is
essential. Many investigations were carried out in identification of putative binding sites of P-gp.
However its translation into rational drug design has not been successful so far. In this study we report an
imperative dynamic trans-membrane model of P-gp that correctly identified the substrate binding residues
of known anticancer agents that reported in experimental studies. The study included homology modeling
of human P-gp based on the crystal structure of murine P-gp, molecular docking, molecular dynamics
analyses, and binding free energy calculations. The model was further utilized to speculate substrate
propensity of novel anticancer compounds. The results showed that one of the anticancer compounds has
absolved P-gp substrate issue, predicting it as a potential lead for anticancer drug devoid of P-gp involved
multiple drug resistance. These predictions results were further validated with Caco-2 cell lines
studies.This model relatively outperforms to delineate drug binding and translocation sites.





DA9// +11. Page .E4

%olecular *ynamics Study o7 .denti7ied Potential .nhi8itors <eads 7or
&f*/F# En2yme: Based on '* Pharmacophore and )irtual Screening
Legesse Adane, Dhilon S. Patel, Sheenu Abbat, Sanchit Dahikar, Prasad V. Bharatam
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER),
Sector-67, S. A. S. Nagar, Mohali, 160062, Punjab, India
Email: pv*haratamCniper.ac.in

Malaria, caused by Plasmodium falciparum, is one of the most prevalent diseases in tropical
regions that kills about 1.5-3 million people annually. Plasmodium falciparum dihydrofolate
reductase (PfDHFR) is an enzyme considered to be one of the most effective targets in the
treatment of malaria. However, point mutations at various active site residues such as Ala16,
Ile51, Cys59, Ser108 and Ile164 in the wild-type have resulted in a widespread resistance against
typical antifolates such as cycloguanil and pyrimethamine. Thus, design and discovery of new
potential PfDHFR inhibitors, active against both the wild-type and mutant strains, is a critical
requirement. A 3D pharmacophore query based on the bioactive conformation of WR99210
extracted from the X-ray crystal structure of quadruple mutant PfDHFR enzyme was generated
using Catalyst software. Pharmacophore based virtual screening was then performed to identify
hits from NCI2000 and Maybridge2004 chemical databases using different filters. The obtained
hits were subjected to FlexX, GOLD and Glide docking programs. The docked compounds were
analyzed based on the binding scores and interactions in the active site of both quadruple-mutant
and wild type PfDHFR. The best one was taken and subjected to molecular dynamics simulation
to study the binding free energy of the compound in both mutant and wild type PfDHFR.

Reference:
Adane, L.; Patel, D.; Bharatam, P. V. Shapeand Chemical FeatureBased 3DPharmacophore
Model Generation and Virtual Screening: Identification of Potential Leads for P. falciparum
DHFR Enzyme Inhibition. Chem. Biol. Drug Des. 2010, 75, 115.
Adane, L.; Bharatam, P. V.; Sharma, V. A common feature-based 3D-pharmacophore model
generation and virtual screening: identification of potential Pf DHFR inhibitors. J. Enzyme Inhib.
Med. Chem. 2010, 25, 635.



DA9// +11. Page .E0

Strategies to identify non Strategies to identify non Strategies to identify non Strategies to identify non- -- -canonical ATP binding sites in proteins canonical ATP binding sites in proteins canonical ATP binding sites in proteins canonical ATP binding sites in proteins
Saravanan Murugeson and Balaji Prakash.
Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016.
ATP, one of the most versatile metabolites in living cells, is utilized by a plethora of
proteins to effect various metabolic functions. The molecule is conformationally flexible and can
bind cognate partners in several unconventional ways - a property which hinders prediction of
how it binds to proteins. In this work, two proteins with hitherto unknown ATP binding sites are
taken which pose two distinct prediction problems. First, predicting the binding site of ATP and
second, predicting the conformation with which it binds. The first protein is HflX, an essential
protein across all kingdoms of life. Recent reports from our laboratory suggest that E.coli HflX
has a novel nucleotide binding domain (ND1) that exhibits significant affinity for ATP despite
the absence of conventional ATP binding motifs[1]. An analysis of ATP binding proteins from a
representative non-redundant dataset showed that glycine, lysine and arginine are the most
abundant residues occurring at 81.7%, 77.8% and 60.2% binding sites respectively. This leads to
a strategy wherein sites with higher density of these residues are located and tested for ATP
binding. Three sites represented by Arg49, Arg103 and Arg99 were thus identified in E.coli
HflX ND1. In case of the second protein - Rel, a stress response protein in bacteria, the
conformation with which ATP binds is unidentified. Rel catalyses the synthesis of (p)ppGpp
from ATP and GTP/GDP. However, in the structure of Rel, Docking softwares failed to identify
a conformation for ATP in the active site, suggesting a flexibile fold. Molecular Dynamics
simulations of the protein with various ligands (substrates and products) were carried out to
study this flexibility. One of the simulations done with ppGpp resulted in the identification of
phosphate binding sites in the protein which inturn led to the prediction of conformation with
which ATP binds at the active site. Using this approach residues important for binding ATP were
identified and confirmed by mutational analysis. Thus, this multifaceted computational approach
could be useful in predicting both the site of ATP binding in proteins and also the conformation
adopted by ATP in the active site pocket.
References References References References
1. Nikhil Jain; Neha Vithani; Abu Rafay; Balaji Prakash. NAR 2013; Identification and characterization
of a hitherto unknown nucleotide-binding domain and an intricate interdomain regulation in HflX-a
ribosome binding GTPase. doi: 10.1093/nar/gkt705 (In press)




DA9// +11. Page .E3


STRUCTURAL INSIGHTS OF DNA - PHARMACEUTICAL BROMINATED
IMPURITY COMPLEX

Prema Awati, Murugesh Easwaran and Shanmughavel Piramanayagam*
Department of Bioinformatics, Bharathiar University, Coimbatore


Background: Pharmaceutical Impurities in API (Active Pharmaceutical Ingredients) and their
profiling is recent target for various regulatory authorities to approve a higher purity percentile
drug. The presence of Impurity may influence the efficacy, safety of pharmaceutical product and
gene mutation if its neurological disorder. Mostly Neurodegenerative Disorders (ND) drugs are
inefficient. Diseases like Alzheimer, Parkinsons, Amyotrophic Lateral Sclerosis (ALS), Autism,
Rett Syndrome have Acetylcholine Esterase (AchE) as target protein to some extent. So we
concentrated on Impurities which are interactable with AchE causing gene mutation. Generally,
there are many sources for a gene mutation, among which Bromine is present in most of NDs
pills. In 2000, Michael et al., inferred that the molecule showing acute sensitivity to AchE is
possible to render gene mutation.

Objectives and Methodology: Drugs and its Pharmacopoeial Impurities are available, aim is to
1. Screen the reference substances and its Impurity containing Bromine. [employing
ChemAxon - Insta J Chem.]
2. Interact the screened Brominated molecule with AchE gene [reported as CD005498 -
HGMD Accession ID] from 81 - 90 bp. [employing Glide module]
3. Simulate the highest affinity complexes for the possible mutation occurrence. [employing
Macromodel module ]

Result and Discussion: Selected 400 molecules include reference substances and its
Pharmacopoeial Impurities among which 56 contain Bromine. Out of 56, 26 molecules are core
and rests are Impurities. The Interaction results showed Ambroxol Impurity ligand possess
highest interaction profile. The DNA undergoes dehelicity during DNA-ligand complex
simulation in water environment as compared to DNA alone in water environment.

Inference: The dehelicity occurrence of DNA-ligand complex infers that the Ambroxol Impurity
is Genotoxic agent, monitoring and profiling of this Impurity during synthesis of Ambroxol is
imperative.




*Corresponding Author

E Mail id
premaawati@rocketmail.com
murugeshphdsch@gmail.com
shanmughavel@buc.edu.in

DA9// +11. Page .E7


In silico modelling, Dynamics and Docking analysis of Protein Kinase Epsilon
in Bipolar disorder
S.Shanthipriya
1
, Vivek Chandramohan
2
, VA Doss
3

1. Research scholar, Department of Bioinformatics, Karpagam University, Coimbatore, India.
2. Department of Biotechnology, Siddaganga Institute of Technology, Tumkur 572103
Karnataka, India
3.Associate professor, Department of Biochemistry, PSG College of Arts & Science,
Coimbatore, India.

Bipolar disorder (BPD) is a condition in which people go back and forth between periods
of a very manic behavior and depression. Recently accumulated evidence indicates that an
alteration in PKC activity plays a significant role in pathophysiology of BPD and its inhibition
plays an important role against BPD. To design antogonists that are effective in treating BPD we
modeled 3D structure of PKC and five models were generated. The model with best PDF total
energy (-9291.1621) and best Dope score (-47210.160156) was selected and analyzed for its
validation using Ramachandran plot and the model was submitted to PMDB (PM0078502).
Potential energy of the modeled protein was analyzed and it was found to be 101265.27565
Kcal/mol and -30972.10032 Kcal/mol respectively. Molecular Dynamics simulation was
performed using Macromodel Version9.0 (Schrodinger module) and OPLS_2005 force field was
used for the energy calculation. Finally, Root Mean Square Deviation (RMSD) was calculated
for checking the stability of target protein with their native motion. The MD simulation was
carried out for the 2WH0 x ray structure, modeled protein and the docked complex to evaluate
the structural stability. While running MD simulation for 2WH0, Modeled protein and Docked
complex, the RMSD plot shows the stability of the complex structures at 80ps. Docking study
was carried out by Biosolve-it. Nine chemical compounds was retrieved and docked. The
Compound Bisindolylmaleimide IX 59H<;A(0+E1 had good Lead It score -24.916 and with
eight H bond interactions.

Key words: Homology modelling, Docking, Bipolar disorder, Molecular Dynamics


DA9// +11. Page .EE


Computational insight into interaction of Pkn3 effector domain with RhoC: A molecular
dynamics study and binding free energy analysis.
Vikash Kumar & M.I.Siddiqi
Molecular & Structural Biology Division, CSIR-CDRI, Lucknow-226030, India.
Emerging role of RhoGTPase in cancer has become attraction centre for exploration of its
interacting partners. It plays pivotal role in cell morphogenesis and movement, hence possible
role in malignancy is accumulating. Interaction of RhoA and PKN1 is known at the structural
level; however their role in cancer is not clear. Recent report of RhoC- PKN3complex in
promoting late stage malignant growth has made this an attractive target for intervention in
cancer progression. Enough experimental evidences are available for RhoC and PKN3
interaction, however structural basis is not known. Here we have attempted in-silico modelling
of RhoC-PKN3 interaction on the basis of sequence analysis and known structure of RhoA and
PKN1 complex. We have carried out molecular dynamics (MD) simulation on in silico modelled
complex of RhoC and PKN3 and analyzed the structural basis of interaction stability .The above
work is a step towards understanding protein-protein interaction(PPI) through MD simulation
and will give an insight into design of PPIs inhibitors as anticancer agents.













DA9// +11. Page *11

Identification of cryptic binding sites of Drp1 using an integrated
computational strategy.
Pradeep Hanumanthappa Bhargy Sharma Rajanikant G. Krishnamurthy
School of Biotechnology National Institute of Technology Calicut Calicut 673601,
India
ABSTRACT:
Mitochondria are one of the dynamic organelles that execute a wide array
of biological functions, critical for the maintenance of cellular homeostasis.
It is evident that mechanisms that impair mitochondrial numbers and volume
within cells will impair signalling pathways, leading to disordered cell
function which manifests as disease. Dynamin related protein1, a highly
conserved profission protein that catalyzes the process of mitochondrial
fission and is also associated with the excessive fragmentation of
mitochondria, impaired mitochondrial dynamics and cell death. Hence,
Dynamin related protein1 is emerging as a key therapeutic target for diseases
involving mitochondrial dysfunction. The most efficacious inhibitor, Mdivi -1, a
cell permeable quinazolinone compound attenuates Drp1 self-assembly by
selectively binding to its allosteric site, thereby reducing mitochondrial fission and
apoptosis. However, the alleged binding site and mechanism of Dynamin
related protein1 inhibition by Mdivi-1 is largely unknown. In this work, we
employ a relatively novel and integrated computational strategy to identify cryptic
binding sites on the Dynamin related protein1 and to delineate the inhibitory
mechanism of Mdivi-1. Our strategy includes the in silico prediction of potential
binding sites, docking, the knowledge based elimination of non-significant
binding sites, and molecular dynamics simulation based selection of most
promising binding site. The results presented here represent a conceptual
advance for comprehending the Drp1-Mdivi interactions and may provide a
crucial guidance for the rational design of more potential and target-specific
Drp1 inhibitors.


DA9// +11. Page *11


STUDY OF DISULFIDE BOND AND DISULFIDE LOOP IN Cu-Zn SOD1
PROTEIN
Keerthana.S.P, and Kolandaivel.P*
Department of Physics, Bharathiar University, Coimbatore-46.
E-mail: ponk,el@hotmail.com

Human Cu-Zn Superoxide Dismutase1 [Cu-Zn SOD1] is a homodimeric protein
that catalyses the dismutation of superoxide Radical to hydrogen peroxide
and oxygen. Each subunit of the homodimer is found to possess two free reduced
cysteines and two oxidized form of cysteines involved in disulfide linkage
Cys-57 and Cys-146. The intra-molecular disulfide bond is found to be very
important in maintaining the rigid structure and enzymatic activity of SOD1. The
function of disulfide bond is not fully elucidated in SOD1 protein. It is also noted
that, the disulfide loop with less number of residues in found have
pronounced effects due to mutation in the protein, while the loop with more
number of residues have no effect. Here we took disulfide bond in SOD1
protein and added additional residues to the terminal of each Cysteine
residues Cys-57 and Cys-146 to identify the variation in the characteristics
of disulfide bond such as bond length and bond energy with the addition of
residues through Quantum Chemical and Molecular Dynamics Simulation
techniques. We also employ atomistic molecular dynamics simulation for a
period of 30ns in polar and vacuum environment to investigate the changes
in the dimer stability of A4V mutation by analyzing the structural variation
and conformational stability of disulfide loop in A4V mutation from Native-
State. The A4v mutation is chosen because among all the mutation it is found to
be very dangerous by reducing the patients life time to a period of one and half
years after diagnosis.


DA9// +11. Page *1+

In silico screening of Traditional Chinese Medicine (TCM) database to
identify leads for Filariasis treatment
Hemant Arya and Mohane S. Coumar*
Centre for Bioinformatics, Pondicherry University, Puducherry-605014, India
*Corresponding : mohane@8icpu.edu.in
Abstract
Lymphatic Filariasis (LF) is a chronic, parasitic and mosquito borne disease
caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori. LF is also
known as Elephantiasis and 120 million people are affected in the world, of
which two-thirds are in Asia. The infection restricts the normal flow of lymph
from the infected area resulting is swelling of extremities, leading to temporary
or permanent disability. Current investigation has shown that available drugs are
getting resistance. Hence, there is an urgent need to find out novel lead
compounds for the treatment of filarial nematodes. In this study we have chosen
asparaginyl-t-RNA synthetases (AsnRS) as a drug target for the inhibition of
filariasis. The main function of AsnRS is to attach asparagine to t-RNA by
two step process and is essential for protein synthesis.
Virtual screening (VS) of 100 natural plant compounds from traditional Chinese
medicines database was carried out using the crystal structure (PDB ID: 2XGT)
of AsnRS in Brugia malayi using Glide module of Schrdinger. The top three
Glide scoring compounds Agri 26 (Tiliroside), Agri 20 (Quercetin 3-
Orhamnopyranosyl) and Agri 1(3-O-beta-D-glucopyranoside), constituent of
Agrimonia pilosa were selected for further Molecular Dynamics (MD)
simulation study. GROMACS 4.6.1 was used for MDsimulation for 20 ns to
examine the stability of the three leads with the AsnRS anti-filarial target. Glu
278, Glu 323, Leu 331 and Arg 321 are the important residues which are
making interaction with lead molecule with the protein in a manner similar to that
of the original ligand (NSS) present in 2XGT. Agri 26 and Agri 20 were forming
stable interactions with the target protein during the 20 ns simulation. Hence the
plant Agrimonia pilosa needs to be tested experimentally to investigate its
potential in anti-filarial assay.
DA9// +11. Page *1.

Identification of HIV1 protease inhibitors through molecular modelling and
structure based virtual screening approach
Dipika Rungta, Nutan Chohan, Swati Kumari and Koel Mukherjee*
Department of Biotechnology, Birla Institute of Technology, Mesra, Ranchi,
Jharkhand- 835215, India
*Corresponding author: Koel Mukherjee, email: koelmukherjee@bitmesra.ac.in;
Tel No: +91 651 227762273
Abstract
HIV-1 protease, a homodimer, has attracted the interest of many researchers due
to its essential role in HIV replication and subsequent functional activities. It
hydrolyses different viral enzymes/proteins into their functional form to help in
maturing the virus for further extending the disease propagation. The present
workflow was designed to identify potential inhibitors for HIV-1 protease. The
in silico binding affinities of existing inhibitors, Atazanavir, Ritonavir and
Noa-His-Hch psi[CH(OH)CH(OH)] Vam-Ile-Amp(U-75875), werecompared using
Glide module in Schrodinger suit 2013. Atazanavir was found to have the highest
affinity (G-score=-12.117) towards HIV-1 protease. Noa-His-Hch psi
[CH(OH)CH(OH)] Vam-Ile-Amp (U-75875) scored the lowest glide score (G-
score=-9.272). The structure based virtual screening on the basis of the binding
modes of best inhibitor was performed and best scoring hits were identified.
The structural behaviour of the best inhibitor-protease complex was validated
through molecular dynamics simulation studies.Simulation studies suggest that the
observed conformational changes in the protease structure might have occurred
due to the binding of the inhibitor molecule. In conclusion, the present structure-
based drug designing approach can be used to enhance more refined inhibitory
property of novel lead molecules against HIV-1 protease that will aid
knowledge in combating AIDS.
Keywords:HIV-1 protease, molecular docking, virtual screening, MD simulation.


DA9// +11. Page *1*

Cyclic peptides as molecular transporters and biosurfactants
Antara Banerjee, Arpita Yadav
Department of chemistry, UIET, CSJM University, Kanpur
1)stract
Cell penetrating peptides are known to self aggregate with or without the presence of
external medium. They have been used for various purposes such as delivery of macromolecules
such as proteins, peptides, oligonucleotides, polysaccharides, nanoparticles and liposomes. They
are known as power tool for non-invasive delivery of cargo inside cell membrane and can be
used for nuclear targeted drugs . They have uses in various industries like cosmetics, detergents,
pharmaceuticals, oils etc. Ab initio Hartree Fock Molecular Orbital calculations have been
performed on some known synthetically prepared cell penetrating peptides. Their use as
molecular transporters have been investigated. They also show artificial membrane formation
which has been investigated at the molecular level. (WR)
5
and (RFEF)
2
have been optimized and
their feasibility to aggregate has been studied. Whether aggregation is spontaneous and
thermodynamically feasible has been determined through intermolecular interaction studies.
Aggregation probability is high in (RFEF)
2
as it can aggregate even in gas phase, keeping both
inner and outer walls hydrophobic; whereas (WR)
5
shows self aggregation only in the presence
of counter-ions and show discrete hydrophobic and hydrophilic surfaces.
Generalization of mode of action of CPPs with their diverse behavioral properties will
facilitate various purposes where there is need for high specificity such as carriage of ions or
drugs across cell membrane or for water treatment of industrial waste etc.


References:
1. Self-assembled surfactant cyclic peptides as stabilizing agents, D. Mandal, R. K. Tiwari, A. N. Shirazi, G.
Ye, A. Banerjee, A. Yadav, K. Parang, Cyclic peptide nanostructures as stabilizing agents, Soft Matter,
DOI:10.1039/b000000x July 2013, in press.
2. Efficient delivery of cell impermeable phosphopetides by a cyclic peptide amphiphiles containing tryptophan
and arginine, A. N. Shirazi, R. K. Tiwari, D. Oh, A. Banerjee, A. Yadav, K. Parang, Molecular
Pharmaceutics, 28 March 2013 DOI: 10.1021/mp400046u.







DA9// +11. Page *14

Behavior of biosurfactant, pepfactant liquid-liquid interface
M. Sonker and A. Yadav*
*epartment o7 hemistry, 0ni,ersity .nstitute o7 Engineering and ;echnology, S+% 0ni,ersity,
(anpur20O024,.ndia, E3mail addresses: %inakshi.Sonker@gmail.com, "rpitayada,@Tahoo.co.in
"8 initio molecular or8ital calculations com8ined 9ith molecular dynamics simulations ha,e 8een
per7ormed on 8iosur7actant .turin ". .ntermolecular interaction results indicate that sel7 aggregation o7
.turin " is thermodynamically 7a,ored e,en in gas phase. .n presence o7 a medium it 9ill 8e 7urther
7acilitated. .n,erted micellar 7ormation is predicted to 8e a spontaneous process and must occur at oil3
9ater inter7ace keeping polar heads to9ards 9ater sur7ace. Sel7 aggregation in #
P
3hexanoyl, a
pep7actant, has also 8een studied 8y intermolecular interaction calculations. #
P
3hexanoyl is a cationic
sur7actant. #esults indicate that it may undergo spontaneous sel7 aggregation induced 8y counterions or
8y change in p/. Elucidation o7 this mode o7 action o7 8iosur7actants and pep7actants 9ill complement
research in designing pep7actants 9ith synthetic ease and industrial applications.
















DA9// +11. Page *10


*rug *esign8 'ynt(esis8 5onformational analysis N *ocking studies of
/ovel 2yrimidine *erivatives: E4pected 1nticancer *rugs
(*ocking8 G-ray and *@9 'tudies"

'a(ag7 13 ;and(i
.
8 -3 ! 2atel
.
8 Hoges( /aliyapara
0
8 *ines( Manavar
0

.
G-ray 5rystallograp(y =a)oratory8 *epartment of 2(ysics8 'ardar 2atel -niversity8 &3&3/agar
0
*epartment of 5(emistry8 'auras(tra -niversity8 ,a7kot

e3mail: sahaLgC@gmail.com, uNhNpatel@yahoo.com

1)stract

Pyrimidine deri,ati,es are 9ell3kno9n nitrogen containing heterocyclic compounds 9hich acting an important role
in medicinal and Pharmaceutical applications. ;he deri,ati,es o7 pyrimidine plays ,ital role in many 8iological
processes and are present in nucleic acid, se,eral ,itamins, co3en2ymes, uric acid and in other nucleic acid. ;hey
7ound to possess anti8acterial, antidepressant, anticon,ulsant, anti3tumor, analgesic, anti3in37lammatory, anti,iral,
anti7ungal and antihistaminic properties. " ne9 series o7 pyrimidine deri,ati,es are designed and synthesi2ed 9ith
the o8Lecti,e o7 de,eloping agents 9ith "nticancer *rugs. ;he Protein3 <igand interaction plays a signi7icant role in
structural 8ased drug designing. ;o understand pharmacological data on structural 8asis, 9e e,aluate the designed
compounds through docking techni:ue. ;he protein structure o7 human estrogen receptor is retrie,ed 7rom P*B
52.>(6. ;he synthesi2ed compounds ha,e 8een con7irmed 8y single crystal H3ray di77raction studies. Ie docked our
designed compounds on Ie ha,e also computed a8 G initio and density 7unctional 5*F;6 calculations using
@aussian 0& so7t9are and omparing the theoretical ,alues 9ith the experimental ones, re,eal similarity 8et9een
optimi2ed 8ond lengths, 8ond angles and torsional angles 9ith H3 ray data. .n addition, molecular or8ital
properties, %uliken charge distri8ution o7 atoms and total energies o7 the title compound ha,e 8een calculated
using #/F and B'<TP methods 9ith the M3'??@ 8asis set.






DA9// +11. Page *13

Computational studies on papaverine self-association in neutral and acidic
conditions
Smriti Khanna, Sampada Koranne, Simon Gaisford, Rajendra Kshirsagar, Nitin Tayade,
Prashant Kameshwar, Koteppa Pari, Chandrika B-Rao, Maneesh Nerrkar
Pirama! "nterprises #td$, % Nir!on Comp!e&, Goregaon '"(, Mm)ai, *++ +,-, .ndia$
Papa/erine hydro0h!oride, is a known antispasmodi0 drg, that shows anoma!os
so!)i!ity )eha/ior nder /arying p1 0onditions$ This has )een attri)ted to se!f-
asso0iation of papa/erine mo!e0!es$
%
2e ha/e attempted to e!0idate the mode of
se!f-asso0iation )y e&perimenta! and 0omptationa! stdies$ "&perimenta! stdies
in/o!/ing %3
%
1 NMR, 43 N5"S6 and P7G-diffsion NMR indi0ated the possi)i!ity of
a dimeri0 state with the two monomers of papa/erine p!a0ed in an antipara!!e!
orientation with respe0t to ea0h other$ Compter sim!ations were 0arried ot in
the hope of gaining additiona! insights into this phenomenon$ Conformationa!
ana!ysis was done sing Ma0romode! mod!e of S0hrodinger for papa/erine dimer$
8ntipara!!e! orientation of the dimer mo!e0!es in non-protonated and protonated
states 'to mimi0 netra! and a0idi0 p1 0onditions, respe0ti/e!y( was sed$ The most
sta)!e 0onformation o)tained from the initia! samp!ing disp!ayed good pi-sta0king
intera0tions )etween the 4 monomers$ Sing!e point dimeri9ation energies in
protonated and non-protonated forms were 0a!0!ated sing :antm me0hani0s
)ased B-#yp method with ,--%G;;<< )asis set in =agar$ 2e fond that
dimeri9ation is energeti0a!!y m0h more fa/ora)!e in so!tion phase than in gas
phase nder a0idi0 0onditions$ So!/ation energy was fond to )e the dri/ing for0e
that promotes dimeri9ation in a0idi0 0onditions with a /ery !ow /a!e '-->$?
k0a!@mo!( for the protonated form 0ompared to non-protonated form '<4$AB
k0a!@mo!(, e&p!aining the phenomena!!y in0reased so!)i!ity$


Referen0eC
%$ Pharma0eti0a! Resear0h, %BA>, Do!me 4, .sse 4, pp ,>-,A$





DA9// +11. Page *17

1 'ingle 'ite mutation (@40D!" 5onverts t(e Enzyme 5H2 0?4 into a !eme
+4ygenase: 1 >MOMM 'tudy

*andamudi 0sharani,
a
ostantino Ea22a,
b
Ien2hen <ai,
a,c
%ukesh hourasia,
a
<ucy Iaskell,
d
Sason
Shaik
a


a
.nstitute o7 hemistry and the <ise3%eitner3%iner,a enter 7or omputational 1uantum
hemistry, ;he /e8re9 0ni,ersity o7 +erusalem, &?&04 +erusalem, .srael

b
entro di Ela8ora2ione dell=.n7orma2ione e del alcolo 5E.6 della Scuola $ormale Superiore di
Pisa Pala22o del astelletto, ,ia del astelletto, ??, PM?2M Pisa, .taly

d
0ni,ersity o7 %ichigan and )" %edical #esearch enter, 22?P Fuller #oad, "nn "r8or, %. 4O?0P,
0S"
1)stract: ;he 9idely distri8uted cytochrome P4P0 class o7 monoxygenases 5TPs6 generates highly
reacti,e oxygen3deri,ed intermediates, 9hich oxidi2e relati,ely inert su8strates in di,erse 9ays. .n
7acilitating di77icult chemical trans7ormations, these en2ymes per7orm important physiological
7unctions such as steroid 8iosynthesis and the meta8olism o7 ingested pharmaceuticals and other
xeno8iotics.
?
@i,en the crucial roles played 8y these en2ymes in human physiology,
understanda8ly there is considera8le interest in gaining the insight into the structural 7actors that
control the reacti,ity. So here 9e present the atomistic 8asis 7or the intriguing incapacitation
2
o7
the TP 2B4 en2yme induced 8y a mutation o7 a single residue, Phe42& to /is, 9hich is explored 8y
means o7 :uantum mechanicalDmolecular mechanical 51%D%%6 calculations o7 the >3>/ 8ond
acti,ation o7 the 5Fe
'F
>>/
3
, pd 06 intermediate. Ie 7ound that the F42&/ mutant o7 TP 2B4
undergoes homolytic, instead o7 heterolytic, >3>/ 8ond clea,age 5Figure ?6. ;his is 8ecause the
mutant ac:uires the 7ollo9ing characteristics o7 a heme oxygenase 5/>6 en2yme: 5a6 ;he donation
o7 an additional /38ond 55$/333S 6 8y /is42& to the cysteine ligand retards the heterolytic clea,age
and gi,es rise to homolytic >3>/ clea,age,
'
and 586 the ;hr'02D9ater cluster and the su8strate
orient the nascent >/
e
close to the meso position o7 the porphyrin, and ensures an e77icient meso
hydroxylation.
4

#e7erences:
?. Shaik, S.! ohen, S.! Iang, T.! hen, /.! (umar, *.! ;hiel, I. 'hem. 2ev. 0C.C, ++#, &4&.
2. *a,ydo,, #.! #a2eghi7ard, #.! .m, S.3.! Iaskell, <.! /o77man. B. %. Biochemistry 0CCE, $1, &MM?.
'. 5a6 Poulos, ;. <. <. Bio(. Inor,. 'hem. .DDP, +, 'PM. 586 >gliaro, F.! de )isser, S. P.! Shaik, S. <. Inor,.
Biochem. 0CC0, J+, PP4.
4. 5a6 %atsui, ;.! 0nno, %.! .keda3Saito, %. Acc. 'hem. 2es. 0C.C, $", 240. 586 hen, /.! %oreau, T.!
*erat, E.! Shaik, S. <. Am. 'hem. Soc. 0CCE, +"#, ?&P'. 5c6 0sharani, *! Ea22a, .! <ai, I. E.!
hourasia, %! Iaskell, <! Shaik, S. <. Am. 'hem. Soc. 0C.0, +"$, 40P'.
DA9// +11. Page *1E

Conformational Preferences in Nateglinide and Stability of its
Complexation with Dendrimer
Vaibhav Jain and Prasad V. Bharatam*

Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER),
Sector 67, S.A.S. Nagar, Mohali 160 062, Punjab, India.

E-mail: jain13.vaibhav@gmail.com
Ab initio (DFT) and semi-empirical (PM3) calculations were performed on the monomer,
dimer and tetramer of antidiabetic drug nateglinide to understand the conformational
preferences and to explore their possible relation with polymorphism. The reported crystal
structure of bis(nateglinide) hydronium chloride shows one asymmetric unit consisting of
four different conformations (Fig. 1a) of the drug. The B3LYP/6-31+G(d,p) optimizations
in gaseous and solvent phase (CPCM model) indicate that these conformers are
energetically quite comparable and the differences disappear in gas phase. Our analysis
shows that (phi) torsion angle of this phenylalanine derivative is responsible for the
observed differences in stability among the nateglinide conformations. The study on the
dimers of nateglinide helps in proposing the structures of polymorphs. The most stable
structure of nateglinide obtained in the solvent phase was utilized to make complexation
with amine terminated G4 PAMAM (G4 PAMAM-NH
2
) and acetylated G4 PAMAM (G4
PAMAM-Ac) dendrimers using molecular docking approach. MD simulation analysis on
complexes revealed that 6 nateglinide molecules can be incorporated in G4 PAMAM-NH
2
,
whereas about 7 nateglinide molecules can be incorporated in G4 PAMAM-Ac. Center-of-
mass separation distance analysis showed that in case of G4 PAMAM-NH
2
drug molecules
are located in the hydrophobic interior pockets of dendrimer, while in case of G4 PAMAM-
Ac most of them are present on surface. Further, MM-PBSA analysis demonstrated that
binding free energies for drug molecules are higher in case of G4 PAMAM-NH
2

(electrostatic + van der Waals interactions) as compared to G4 PAMAM-Ac (only van der
Waals interactions). This computational study illustrated that nateglinide forms stable
complexation with G4 PAMAM dendrimers and thus, can be effectively used to overcome
the existing limitations of nateglinide like solubility and can also render sustained release
action.







DA9// +11. Page *11

Vibrational and Non Linear Analysis Uracil using First Principle Method
Vijay Narayan
1
, Amarendra Kumar
2

1: Department of Physics
Sri Ramswaroop Memorial Group of Professional Colleges
Tewariganj, Faizabad Road, Lucknow-227105
Uttar Pradesh
INDIA

2: Department of Physics
University of Lucknow
Lucknow-227105
Uttar Pradesh
INDIA

Email : vnvictorious@gmail.com
Abstract:
Uracil is the one the four nucleo38ases in the nucleic acid of #$" . Uracil is a naturally
occurring pyrimidine derivative has planar, unsaturated compound that has the ability to absorb light and
used for drug deli,ery and as a pharmaceutical.Uracil derivatives containing a dia2inering are used
in pesticides. The present communication deals with the investigation of the structural, electronic and
vibrational properties of uracil. The structure and harmonic wavenumbers have been determined and
analyzed at DFT level employing the basis set 6-311++G(d,p). The optimized geometry of uracil and its
molecular properties such as equilibrium energy, frontier orbital energy gap, molecular electrostatic
potential energy map, dipole moment, polarizability, and first static hyperpolarizability have been
calculated and discussed. The NLO activity of uracil has been reported for the first time.The present
study of uracil ,in general may lead to the better understanding of the relationship between the molecular
architecture/ structure and non linear response in terms of hyperpolarizability and its vibrational modes
and may help in designing and synthesizing new efficient materials for technological applications.
Key words: Uracil, Density functional theory, NLO activity




DA9// +11. Page *11


Computational Modeling of Spin state Dependent Reactivity of
Bio-Inspired Model Complexes of Mononuclear Non-Heme Enzymes

M. Jaccob
Department of Chemistry, Loyola College, Chennai 600 034, Tamil Nadu, India
Email: ma%havan)ack#!C,mai(.com

Activation and chemical transformation of molecular oxygen is a crucial process in biologically
important chemical reactions. In nature, metalloenzymes use diverse active sites such as heme
and non-heme (mono- and dinuclear) iron sites to activate dioxygen.
1
High-valent iron-oxo
intermediates are found to be the active species in the catalytic cycles of oxygenation reactions.
These intermediates can be also found to promote a broad range of synthetically and industrially
relevant reactions such as hydroxylation, epoxidation, cis-dihydroxylation, heterocyclic ring
formation and oxidative aromatic ring cleavage.
2
In order to tune the efficiency and selectivity of
the oxidation catalyst, we need to evaluate the catalytic mechanisms of the enzymes under
scrutiny in detail. On the basis of experimental and computational mechanistic investigations,
various close-lying spin states of high-valent ferryl-oxo complexes are energetically accessible
and this may lead to spin-crossover. The product distribution and yield depend not only on the
ground but also on excited states (two- or multistate reactivity). Experimental proof for reaction
mechanism involving various spin states is not a simple matter and in such a situation,
computational chemistry has been playing an essential role in providing mechanistic data and
structural information about unstable intermediates involving various spin states.
3
In this poster, I
would like to present the overview about the spin state dependent reactivity of bio-inspired
model complexes using DFT methods [(L)M
IV
=X (where M = Fe, Mn ; X = O, NTs; L =
bispidine, H
5
buea and H
3
bupa ligands].
4
With the help of computation, we have shown that one
can control the relative height of activation energy barriers upon modifying the steric and
electronic factors of ligand skeletons. This paved a way to tune their catalytic selectivity and
efficiency of the oxidation catalysts and these predictions can lead to the new experimental
studies.

References:
1. a) A. Gunay and K. H. Theopold, Chem. Rev. 2010, 110, 1060. b) W. Nam, Acc. Chem. Res.,
2007, 40, 522-531.
2. a) B. Meunier, S. P. de Visser and S. Shaik, Chem. Rev. 2004, 104, 3947.; b) L. Que, Jr. and
R. Y. N. Ho, Chem. Rev. 1996, 96, 26072624.
3. Hirao, H.; Kumar, D.; Que, L. Jr.; Shaik, S., J. Am. Chem. Soc, 2006, 128, 8590.
4. M. Jaccob et al, Dalton Trans., 2011, 40, 11276-11281.; Dalton Trans. 2012, 41, 10430-
10439; Dalton Trans., 2013, accepted.