Molecular docking is a prevalent tool in drug discovery. DOCK 6's extensible design enables implementing and testing new methods in molecular docking. Development in DOCK 3 enabled screening of large databases of billions of small molecules. To allow access to this unprecedented chemical space, we have implemented features from DOCK 3.7 into DOCK 6, including traversal of precomputed ligand conformations stored in a hierarchical database. We test these new features retrospectively.

Abstract

To allow DOCK 6 access to unprecedented chemical space for screening billions of small molecules, we have implemented features from DOCK 3.7 into DOCK 6, including a search routine that traverses precomputed ligand conformations stored in a hierarchical database. We tested them on the DUDE-Z and SB2012 test sets. The hierarchical database search routine is 16 times faster than anchor-and-grow. However, the ability of hierarchical database search to reproduce the experimental pose is 16% worse than that of anchor-and-grow. The enrichment performance is on average similar, but DOCK 3.7 has better enrichment than DOCK 6, and DOCK 6 is on average 1.7 times slower. However, with post-docking torsion minimization, DOCK 6 surpasses DOCK 3.7. A large-scale virtual screen is performed with DOCK 6 on 23 million fragment molecules. We use current features in DOCK 6 to complement hierarchical database calculations, including torsion minimization, which is not available in DOCK 3.7.