Journal ArticleDOI
Improving structure-based virtual screening by multivariate analysis of scoring data.
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TLDR
A new two-stage approach is suggested for structure-based virtual screening where limited activity information is available and the classifiers show a superior performance, with rule-based methods being most effective.Abstract:
Three different multivariate statistical methods, PLS discriminant analysis, rule-based methods, and Bayesian classification, have been applied to multidimensional scoring data from four different target proteins: estrogen receptor α (ERα), matrix metalloprotease 3 (MMP3), factor Xa (fXa), and acetylcholine esterase (AChE) The purpose was to build classifiers able to discriminate between active and inactive compounds, given a structure-based virtual screen Seven different scoring functions were used to generate the scoring matrices The classifiers were compared to classical consensus scoring and single scoring functions The classifiers show a superior performance, with rule-based methods being most effective The precision of correctly predicting an active compound is about 90% for three of the targets and about 25% for acetylcholine esterase On the basis of these results, a new two-stage approach is suggested for structure-based virtual screening where limited activity information is availableread more
Citations
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Journal ArticleDOI
Benchmarking sets for molecular docking.
TL;DR: A directory of useful decoys (DUD), with 2950 ligands for 40 different targets, leading to a database of 98,266 compounds, which allowed 40x40 cross-docking, where the enrichments of each ligand set could be compared for all 40 targets, enabling a specificity metric for the docking screens.
Journal ArticleDOI
Virtual screening workflow development guided by the "receiver operating characteristic" curve approach. Application to high-throughput docking on metabotropic glutamate receptor subtype 4.
TL;DR: Characterizing both the ability of a virtual screening workflow to select active molecules and the ability to discard inactive ones, the ROC curve approach is well suited for this critical decision gate.
Journal ArticleDOI
DrugScore(CSD)-knowledge-based scoring function derived from small molecule crystal data with superior recognition rate of near-native ligand poses and better affinity prediction.
TL;DR: A necessary prerequisite to successfully resolving the scoring problem with a more discriminative scoring function is the generation of highly accurate ligand poses, which approximate the native pose to below 1 angstroms rmsd, in a docking run.
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?
TL;DR: 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.
Journal ArticleDOI
Receptor–ligand molecular docking
TL;DR: The main topics and recent computational and methodological advances in protein–ligand docking are summarised, including protein flexibility, multiple ligand binding modes and the free-energy landscape profile for binding affinity prediction.
References
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On the Optimality of the Simple Bayesian Classifier under Zero-One Loss
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A Fast Flexible Docking Method using an Incremental Construction Algorithm
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A geometric approach to macromolecule-ligand interactions
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