Automated Virtual Screening

Computational methods in modern drug discovery have become ubiquitous, with methods that cover most of the discovery stages: from hit finding and lead identification to lead optimization. The overall aim of these computational methods is to obtain a more efficient discovery process, by reducing the number of “wet” experiments required to produce therapeutics that have higher probability of succeeding in clinical development and subsequently benefitting end patients by developing highly effective therapeutics having minimal side effects. Virtual Screening is usually applied at the early stage of drug discovery, looking to find chemical matter having desired properties, such as molecular shape, electrostatics, and pharmacophores at desired three-dimensional positions. The aim of this stage is to search in a wide chemical space, including chemistry available from commercial suppliers and virtual databases of predicted reaction products, to identify molecules that would exert a particular biochemical response. This initial stage of the discovery process is very important since the subsequent stages will use the initial chemical motifs that have been found at the hit finding stage, and therefore the most suitable the compound is found, the more likely it is that subsequent stages will be successful and less time and resource consuming. This chapter provides a summary of various Virtual Screening methods, including shape match and molecular docking, and these methods are used in a Virtual Screening workflow that is provided as an example which is described to be run automatically in cloud resources. This automatic in-depth exploration of the chemical space using validated Virtual Screening methods can lead to a more streamlined and efficient discovery process, aiming to deliver chemical matter of high quality and maximizing the required biological effects while minimizing adverse effects. Surely, Virtual Screening pipelines of this nature will continue to play a central role in producing much needed therapeutics for the health challenges of the future.