Benchmarking sets for molecular docking.

Niu Huang; Brian K Shoichet; John J Irwin

doi:10.1021/jm0608356

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Benchmarking sets for molecular docking.

Niu Huang·Brian K Shoichet·John J Irwin

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Abstract

Ligand enrichment among top-ranking hits is a key metric of molecular docking. To avoid bias, decoys should resemble ligands physically, so that enrichment is not simply a separation of gross features, yet be chemically distinct from them, so that they are unlikely to be binders. We have assembled a directory of useful decoys (DUD), with 2950 ligands for 40 different targets. Every ligand has 36 decoy molecules that are physically similar but topologically distinct, leading to a database of 98,266 compounds. For most targets, enrichment was at least half a log better with uncorrected databases such as the MDDR than with DUD, evidence of bias in the former. These calculations also 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. DUD is freely available online as a benchmarking set for docking at http://blaster.docking.org/dud/.

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Adenosine Deaminase Aldehyde Reductase Binding Sites Databases, Factual Drug Design Inhibins Ligands Models, Molecular Pharmaceutical Preparations Protein Binding Protein Conformation Proteins Quantitative Structure-Activity Relationship Receptors, Estrogen Thymidine Kinase p38 Mitogen-Activated Protein Kinases Journal Article Research Support, N.I.H., Extramural

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Niu Huang, Brian K Shoichet, John J Irwin. 2006-11-16. Benchmarking sets for molecular docking.. https://doi.org/10.1021/jm0608356

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