Systematic exploitation of multiple receptor conformations for virtual ligand screening.

ABSTRACT: The role of virtual ligand screening in modern drug discovery is to mine large chemical collections and to prioritize for experimental testing a comparatively small and diverse set of compounds with expected activity against a target. Several studies have pointed out that the performance of virtual ligand screening can be improved by taking into account receptor flexibility. Here, we systematically assess how multiple crystallographic receptor conformations, a powerful way of discretely representing protein plasticity, can be exploited in screening protocols to separate binders from non-binders. Our analyses encompass 36 targets of pharmaceutical relevance and are based on actual molecules with reported activity against those targets. The results suggest that an ensemble receptor-based pro

SUBMITTER: Bottegoni G 

PROVIDER: S-EPMC3098722 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature