Virtual Screening for HIV Protease Inhibitors Using a Novel Database Filtering Procedure

A virtual screening to find novel inhibitors for HIV protease was performed on the ZINC database.1 A critical part in virtual screening and associated techniques is preliminary database filtering and size reduction and for that purpose a novel feature matrix matching procedure was used. The reduction of ∼14 million available ligands to a subset of 14299 ligands was achieved with a structure based approach where the analysis of the 3D structure of the active site of the protease produced a graph with hydrogen bond donor, hydrogen bond acceptor and hydrophobic subsites represented as graph nodes. A similar treatment was also applied to the compound database content and the comparison of binding site and ligand graphs was used to preselect potentially active ligands. The resulting set was further subjected to docking. The algorithm used was able to find several novel as well as previously known and experimentally tested ligands, demonstrating the validity of the approach.