Compound selection for virtual screening

Abstract

VS has emerged as an adaptive response [2] to the massive throughput drug discovery machine (such as high throughput screening, [HTS] and combinatorial chemistry), which has pressured the computational chemistry community to rapidly evaluate billions of virtual (that is, existing in silico only) molecules and to assist synthesis prioritization and HTS analyses. In fairness, VS is just one of the cornerstone technologies of the novel drug discovery paradigm, briefly outlined below: • Large numbers of preplated compounds are tested, typically under singledose/single-experiment conditions, in what constitutes a HTS experiment. Compounds that show activity in this process are designated as HTS hits • The HTS hits are subsequently retested to confirm activity and structure; the reason for structural confirmation relates to the combinatorial or the commercial history of any particular molecule (or both). The usual success rate for single-dose HTS is under 0.1%.