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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: [email protected]
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 [email protected] ,[email protected]
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: [email protected] & [email protected]
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