In pursuit of virtual lead optimization: pruning ensembles of receptor structures for increased efficiency and accuracy during docking.

ABSTRACT: Representing receptors as ensembles of protein conformations during docking is a powerful method to approximate protein flexibility and increase the accuracy of the resulting ranked list of compounds. Unfortunately, docking compounds against a large number of ensemble members can increase computational cost and time investment. In this article, we present an efficient method to evaluate and select the most contributive ensemble members prior to docking for targets with a conserved core of residues that bind a ligand moiety. We observed that ensemble members that preserve the geometry of the active site core are most likely to place ligands in the active site with a conserved orientation, generally rank ligands correctly and increase interactions with the receptor. A relative distance appro

SUBMITTER: Bolstad ES 

PROVIDER: S-EPMC2649978 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature