Virtual screening

Virtual screening ("VS") has become an integral part of the drug discovery process in recent years. Related to the more general and long pursued concept of database searching, the term "virtual screening" is relatively new. Walters, et al. define virtual screening as "automatically evaluating very large libraries of compounds" using computer programs. As this definition suggests, VS has largely been a numbers game focusing on questions like how can we filter down the enormous chemical space of over 1060 conceivable compounds to a manageable number that can be synthesized, purchased, and tested. Although filtering the entire chemical universe might be a fascinating question, more practical VS scenarios focus on designing and optimizing targeted combinatorial libraries and enriching libraries of available compounds from in-house compound repositories or vendor offerings.

The main goal of a virtual screen is to come up with hits of novel chemical structure that yield a unique pharmacological profile. Thus, success of a virtual screen is defined in terms of finding interesting new scaffolds rather than many hits. Interpretations of VS accuracy should therefore be considered with caution. Low hit rates of interesting scaffolds are clearly preferable over high hit rates of already known scaffolds.