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 npi* 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 npi* 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

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.SUVAITHENAMUDHAN 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 Kamala,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 inhibitors1, 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 elucidated3. 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 Prime4 module. Based on known critical functional residues3, 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 GLIDE4 module. The pharmacophore hypothesis thus developed was used to screen against the TosLab database (7000 filtered drug-like compounds) using PHASE4.

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 Basappaa,b,

aLaboratory of Chemical Biology, Department of Chemistry, Bangalore University, Palace Road, Bangalore-560001, India

bUnilever 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