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

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.