Journal ArticleDOI
Evaluation of the performance of 3D virtual screening protocols: RMSD comparisons, enrichment assessments, and decoy selection—What can we learn from earlier mistakes?
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TLDR
This review analyzes recent literature evaluating 3D virtual screening methods, with focus on molecular docking, and highlights problematic issues and provides guidelines on how to improve the quality of computational studies.Abstract:
Within the last few years a considerable amount of evaluative studies has been published that investigate the performance of 3D virtual screening approaches. Thereby, in particular assessments of protein-ligand docking are facing remarkable interest in the scientific community. However, comparing virtual screening approaches is a non-trivial task. Several publications, especially in the field of molecular docking, suffer from shortcomings that are likely to affect the significance of the results considerably. These quality issues often arise from poor study design, biasing, by using improper or inexpressive enrichment descriptors, and from errors in interpretation of the data output. In this review we analyze recent literature evaluating 3D virtual screening methods, with focus on molecular docking. We highlight problematic issues and provide guidelines on how to improve the quality of computational studies. Since 3D virtual screening protocols are in general assessed by their ability to discriminate between active and inactive compounds, we summarize the impact of the composition and preparation of test sets on the outcome of evaluations. Moreover, we investigate the significance of both classic enrichment parameters and advanced descriptors for the performance of 3D virtual screening methods. Furthermore, we review the significance and suitability of RMSD as a measure for the accuracy of protein-ligand docking algorithms and of conformational space sub sampling algorithms.read more
Citations
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Journal ArticleDOI
ZINC 15 – Ligand Discovery for Everyone
Teague Sterling,John J. Irwin +1 more
TL;DR: A suite of ligand annotation, purchasability, target, and biology association tools, incorporated into ZINC and meant for investigators who are not computer specialists, offer new analysis tools that are easy for nonspecialists yet with few limitations for experts.
Journal ArticleDOI
Molecular Docking and Structure-Based Drug Design Strategies
TL;DR: The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods.
Journal ArticleDOI
Advances and Challenges in Protein-Ligand Docking
Sheng-You Huang,Xiaoqin Zou +1 more
TL;DR: Recent advances of protein flexibility, ligand sampling, and scoring functions—the three important aspects in protein-ligand docking are reviewed.
Journal ArticleDOI
Comparison of several molecular docking programs: pose prediction and virtual screening accuracy.
Jason B. Cross,David C. Thompson,Brajesh K. Rai,J. Christian Baber,Kristi Fan,Yongbo Hu,Christine Humblet +6 more
TL;DR: Cognate ligand docking to 68 diverse, high-resolution X-ray complexes revealed that ICM, GLIDE, and Surflex generated ligand poses close to the X-rays conformation more often than the other docking programs.
Journal ArticleDOI
Recognizing Pitfalls in Virtual Screening: A Critical Review
Thomas Scior,Andreas Bender,Gary Tresadern,José L. Medina-Franco,Karina Martinez-Mayorga,Thierry Langer,Karina Cuanalo-Contreras,Dimitris K. Agrafiotis +7 more
TL;DR: This review attempts to catalogue published and unpublished problems, shortcomings, failures, and technical traps of VS methods with the aim to avoid pitfalls by making the user aware of them in the first place.
References
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Journal ArticleDOI
The Protein Data Bank
Helen M. Berman,John D. Westbrook,Zukang Feng,Gary L. Gilliland,Talapady N. Bhat,Helge Weissig,Ilya N. Shindyalov,Philip E. Bourne +7 more
TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.
Journal ArticleDOI
Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy.
Richard A. Friesner,Jay L. Banks,Robert B. Murphy,Thomas A. Halgren,Jasna Klicic,Daniel T. Mainz,Matthew P. Repasky,Eric H. Knoll,Mee Shelley,Jason K. Perry,David E. Shaw,Perry Francis,Peter S Shenkin +12 more
TL;DR: Glide approximates a complete systematic search of the conformational, orientational, and positional space of the docked ligand to find the best docked pose using a model energy function that combines empirical and force-field-based terms.
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Development and validation of a genetic algorithm for flexible docking.
TL;DR: GOLD (Genetic Optimisation for Ligand Docking) is an automated ligand docking program that uses a genetic algorithm to explore the full range of ligand conformational flexibility with partial flexibility of the protein, and satisfies the fundamental requirement that the ligand must displace loosely bound water on binding.
Journal ArticleDOI
Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening.
Thomas A. Halgren,Robert B. Murphy,Richard A. Friesner,Hege S. Beard,Leah L. Frye,W. Thomas Pollard,Jay L. Banks +6 more
TL;DR: Comparisons to results for the thymidine kinase and estrogen receptors published by Rognan and co-workers show that Glide 2.5 performs better than GOLD 1.1, FlexX 1.8, or DOCK 4.01.
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Comparison of the predicted and observed secondary structure of T4 phage lysozyme.
TL;DR: Although empirical predictions based on larger numbers of known protein structure tend to be more accurate than those based on a limited sample, the improvement in accuracy is not dramatic, suggesting that the accuracy of current empirical predictive methods will not be substantially increased simply by the inclusion of more data from additional protein structure determinations.
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