Structure-based approaches to drug design and virtual screening

Structure-based design has made an important contribution to drug discovery for many years. Recently, the increasing availability of structural data and the affordability of high-performance computing platforms have broadened the applicability of these methods. In particular, virtual screening has been adopted as an effective paradigm for lead discovery that fits in well alongside high-throughput screening programs. Structure-based virtual screening relies on fast and accurate computational methods for the prediction of receptor-ligand binding modes and binding affinities. In this paper, recent technical advances in the field of molecular docking and de novo design are reviewed, in particular, the development of flexible receptor models, docking of combinatorial libraries and novel scoring methods.