The holistic integration of virtual screening in drug discovery

► We observe an advanced level of maturation of virtual screening in drug discovery. ► Virtual screening is not applied distinctly to other hit finding techniques. ► In recent studies it is used complementary with different grades of integration. ► We propose a classification of integration levels of virtual screening in drug discovery. ► The classification will help documenting and supporting future developments. During the past decade, virtual screening (VS) has come of age. In this review, we document the evolution and maturation of VS from a rather exotic, stand-alone method toward a versatile hit and lead identification technology. VS campaigns have become fully integrated into drug discovery campaigns, evenly matched and complementary to high-throughput screening (HTS) methods. Here, we propose a novel classification of VS applications to help to monitor the advances in VS and to support future improvement of computational hit and lead identification methods. Several relevant VS studies from recent publications, in both academic and industrial settings, were selected to demonstrate the progress in this area. Furthermore, we identify challenges that lie ahead for the development of integrated VS campaigns.