Benchmarking Sets for Molecular Docking

TLDR

Ligand enrichment among top‑ranking hits is a key metric of molecular docking, and decoys must physically resemble ligands to avoid bias while remaining chemically distinct to prevent false positives. The authors constructed a database of 98,266 compounds by pairing each of 2,950 ligands with 36 physically similar but topologically distinct decoys, and performed 40×40 cross‑docking to compare enrichments across all 40 targets and derive a specificity metric. The authors assembled the DUD directory of 2,950 ligands for 40 targets, found that uncorrected databases like MDDR yielded at least half a log higher enrichment than DUD—indicating bias—and made DUD freely available online at http://blaster.docking.org/dud/.

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 40 × 40 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/.