DOCK 6: Incorporating hierarchical traversal through precomputed ligand conformations to enable large‐scale docking

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.