The Science and Art of Structure-Based Virtual Screening

Abstract

Structure-based virtual screening has gained momentum again as the high attrition rate at every stage of drug discovery drives the need to explore a greater chemical space. From the Bayesian perspective, its shortcomings as a viable strategy for sustainable hit discovery are discussed, with regard to the prior hit rates of screening libraries and the performance of computational methods. Lessons are shared in selecting virtual hits for experimental validation learned from a series of eight successful campaigns, one of which impacted the discovery of a drug candidate currently in clinical trials.