title: Benchmarking sets for molecular docking.
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/.
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco, QB3 Building, 1700 4th Street, Box 2550, San Francisco, California 94143-2550, USA.
authors.forename: Niu
authors.initials: N
authors.lastname: Huang
authors.forename: Brian K
authors.initials: BK
authors.lastname: Shoichet
authors.forename: John J
authors.initials: JJ
authors.lastname: Irwin
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry; D000449:Aldehyde Reductase / Q000737:chemistry; D001665:Binding Sites; D016208:Databases, Factual; D015195:Drug Design; D007265:Inhibins / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000737:chemistry; D013937:Thymidine Kinase / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000737:chemistry
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D011506:Proteins; D011960:Receptors, Estrogen; C094377:inhibin-alpha subunit; D007265:Inhibins; D000449:Aldehyde Reductase; D013937:Thymidine Kinase; D048051:p38 Mitogen-Activated Protein Kinases; D000243:Adenosine Deaminase