2.7.1 In-Silico Screening

In-silico (computational) screening allows enormous virtual compound libraries — commonly tens of millions of commercially available or synthetically...

In-silico (computational) screening allows enormous virtual compound libraries — commonly tens of millions of commercially available or synthetically accessible structures — to be evaluated computationally against a target of interest before a single physical compound is purchased or synthesised. Virtual screening approaches are broadly divided into structure-based methods, which require a resolved or homology-modelled three-dimensional structure of the target, and ligand-based methods, which instead exploit the structural features of known active compounds (via pharmacophore modelling or quantitative structure-activity relationship, QSAR, analysis) to prioritise structurally similar candidates from a virtual library. The principal advantage of in-silico screening is economy: it allows a research programme to concentrate scarce synthetic and biological screening resources on the small subset of compounds most likely to show genuine activity, dramatically improving hit rates relative to purely random physical screening.