Virtual Ligand Screening for Structure-based Drug Design: Approaches and Progress

Recent progress in human genomics and proteomics has significantly increased the number of macromolecular targets potentially involved in drug discovery campaigns. Today technologies like combinatorial chemistry and high-throughput screening (HTS) authorize biological assays of a large number of small molecules against the therapeutically relevant targets. However the escalating costs highlight the need of developing novel approaches while still allowing one to explore larger chemical diversity. In this respect, virtual ligand screening (VLS) is established as an attractive approach to handle large sets of compounds and to improve the “hit-rate” of drug discovery programs. Here, we review the main VLS techniques applied for structure-based drug design and we focus on key concepts in the molecular docking–scoring methodology.