Journal Article10.1038/NRD1549
Docking and scoring in virtual screening for drug discovery: methods and applications.
TL;DR: Key concepts and specific features of small-molecule–protein docking methods are reviewed, selected applications are highlighted and recent advances that aim to address the acknowledged limitations of established approaches are discussed.
read more
Abstract: Computational approaches that 'dock' small molecules into the structures of macromolecular targets and 'score' their potential complementarity to binding sites are widely used in hit identification and lead optimization Indeed, there are now a number of drugs whose development was heavily influenced by or based on structure-based design and screening strategies, such as HIV protease inhibitors Nevertheless, there remain significant challenges in the application of these approaches, in particular in relation to current scoring schemes Here, we review key concepts and specific features of small-molecule-protein docking methods, highlight selected applications and discuss recent advances that aim to address the acknowledged limitations of established approaches
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
Garrett M. Morris,Ruth Huey,William Lindstrom,Michel F. Sanner,Richard K. Belew,David S. Goodsell,Arthur J. Olson +6 more
TL;DR: AutoDock4 incorporates limited flexibility in the receptor and its utility in analysis of covalently bound ligands is reported, using both a grid‐based docking method and a modification of the flexible sidechain technique.
21.1K
Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments
TL;DR: It is shown that database enrichment is improved with proper preparation and that neglecting certain steps of the preparation process produces a systematic degradation in enrichments, which can be large for some targets.
5K
Drug repurposing: progress, challenges and recommendations
Sudeep Pushpakom,Francesco Iorio,Patrick A. Eyers,K. Jane Escott,Shirley Hopper,Andrew D. Wells,Andrew J. Doig,Tim Guilliams,Joanna Latimer,Christine J. McNamee,Alan Norris,Philippe Sanseau,David Cavalla,Munir Pirmohamed +13 more
TL;DR: Approaches used for drug repurposing (also known as drug repositioning) are presented, the challenges faced by the repurpose community are discussed, and innovative ways by which these challenges could be addressed are recommended to help realize the full potential of drugRepurposing.
3.7K
Molecular docking: a powerful approach for structure-based drug discovery.
TL;DR: This review presents a brief introduction of the available molecular docking methods, and their development and applications in drug discovery, and a recently developed local move Monte Carlo based approach is introduced.
Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking
TL;DR: An improved benchmarking set that includes more diverse targets such as GPCRs and ion channels, totaling 102 proteins with 22886 clustered ligands drawn from ChEMBL, each with 50 property-matched decoys drawn from ZINC, is described.
2.1K
References
Analyses of Activity for Factor Xa Inhibitors Based on Monte Carlo Simulations
TL;DR: The two factors that emerged as important in determining inhibitory potential are favorable van der Waals interactions between protein and ligand and direct hydrogen bonding between the inhibitor and protein.
27
GroupBuild: a fragment-based method for de novo drug design
Sergio H. Rotstein,Murcko Mark A +1 more
TL;DR: GroupBuild as mentioned in this paper is a method for de novo drug design, which is composed entirely of individual functional groups (also known as "building blocks" or "fragments") which the program chooses from a predefined library.
26
•Journal Article
Small molecule recognition: solid angles surface representation and molecular shape complementarity.
TL;DR: Dock 185 receptor-small ligand molecule pairs and find that such a representation performs adequately for the smaller ligands too, and that shape complementarity is also observed.
24
Identification of a novel class of inhibitor of human and Escherichia coli thymidine phosphorylase by in silico screening
V McNally,Abdul M Gbaj,Kenneth T. Douglas,Ian J. Stratford,Mohammed Jaffar,Sally Freeman,Richard A. Bryce +6 more
TL;DR: Structure-based computational screening of the National Cancer Institute database of anticancer compounds identified novel non-nucleobase-derived inhibitors of human thymidine phosphorylase as candidates for lead optimization as well as potentially strong low molecular weight ligands exhibiting a range of molecular scaffolds.
20
A simple method for visualizing the differences between related receptor sites.
Robert P. Sheridan,M. Katharine Holloway,Georgia B. McGaughey,Ralph T. Mosley,Suresh B. Singh +4 more
TL;DR: FLOGTV, based on the trend vector paradigm, is presented, which is mathematically simpler than the GRID/CPCA method of Kastenholz et al. and allows for the simultaneous comparison of many receptor structures.
18