Use of an Induced Fit Receptor Structure in Virtual Screening

Abstract

Structured-based drug design has traditionally relied on a single receptor structure as a target for docking and screening studies. However, it has become increasingly clear that in many cases where protein flexibility is an issue, it is critical to accurately model ligand-induced receptor movement in order to obtain high enrichment factors. We present a novel protein-ligand docking method that accounts for both ligand and receptor flexibility and accurately predicts the conformation of protein-ligand binding complexes. This method can generate viable receptor ensembles that can be used in virtual database screens.