Protein–Ligand Docking: Virtual Screening and Applications to Drug Discovery

The term virtual screening (VS) was rst reported in literature in 1997 (Horvath 1997), and refers to computational techniques aimed at streamlining the drug discovery process through in silico identication of novel hits from large chemical libraries. In the early 1990s, the drug discovery paradigm was overturned by the introduction of high-throughput screening (HTS) (Bleicher et al. 2003) and combinatorial chemistry (Geysen et al. 2003). These techniques promised to accelerate the drug discovery process by enabling the synthesis of large libraries of chemical compounds and the assay of their biological activity against several targets in a short period of time. However, the revolutionary approach soon proved to be expensive and not productive as expected, as many of the identied hits failed the lead optimization stage due to unsuitable pharmacokinetic properties. The development of alternative strategies to select appropriate compounds, while removing unsuitable structures, aimed at si...