Eight docking programs (DOCK, FLEXX, FRED, GLIDE, GOLD, SLIDE, SURFLEX, and QXP) that can be used for either single-ligand docking or database screening have been compared for their propensity to recover the X-ray pose of 100 small-molecular-weight ligands, and for their capacity to discriminate known inhibitors of an enzyme (thymidine kinase) from randomly chosen "drug-like" molecules. Interestingly, both properties are found to be correlated, since the tools showing the best docking accuracy (GLIDE, GOLD, and SURFLEX) are also the most successful in ranking known inhibitors in a virtual screening experiment. Moreover, the current study pinpoints some physicochemical descriptors of either the ligand or its cognate protein-binding site that generally lead to docking/scoring inaccuracies.
Copyright 2004 Wiley-Liss, Inc.