High-performance drug discovery: computational screening by combining docking and molecular dynamics simulations.

ABSTRACT: Virtual compound screening using molecular docking is widely used in the discovery of new lead compounds for drug design. However, this method is not completely reliable and therefore unsatisfactory. In this study, we used massive molecular dynamics simulations of protein-ligand conformations obtained by molecular docking in order to improve the enrichment performance of molecular docking. Our screening approach employed the molecular mechanics/Poisson-Boltzmann and surface area method to estimate the binding free energies. For the top-ranking 1,000 compounds obtained by docking to a target protein, approximately 6,000 molecular dynamics simulations were performed using multiple docking poses in about a week. As a result, the enrichment performance of the top 100 compounds by our approach

SUBMITTER: Okimoto N 

PROVIDER: S-EPMC2746282 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature