Virtual screening in lead discovery and optimization.

Virtual screening by molecular docking, using a protein with an experimentally determined structure as a target, has become an established method for lead discovery and for enhancing efficiency in lead optimization. Generalizations of the quantitative structure-activity relationship concept have led to approaches for virtual screening in the absence of a protein target structure, instead relying upon ligand-based models as surrogates of protein active sites. Recently reported methods for ligand-based virtual screening can achieve similar enrichment rates to those obtained using molecular docking. This review will discuss recent advances in both domains of virtual screening, including theoretical and practical advances and the implications for their application.