Making virtual screening a reality
John T. Koh · Proceedings of the National Academy of Sciences · 2003
The discovery of new bioactive compounds for specific biomolecular targets represents a significant hurdle in the early stages of drug discovery. Advances in automation and bioanalytical methods have provided high-throughput screening (HTS) techniques that can perform individual biochemical assays on as many as a million compounds or more. Even with HTS, the discovery of new lead compounds largely remains a matter of trial and error. Although the number of compounds that can be evaluated by HTS methods is seemingly large, these numbers are small in comparison to the astronomical number of possible molecular structures that might represent potential drug-like molecules (1). Often, far more compounds exist or can be synthesized by combinatorial methods than can be reasonably and affordably evaluated by HTS. As the costs of computing decreases and as computational speeds increase, many researchers have directed efforts to develop computational methods to perform “virtual screens” of compounds (2–4). Because the cost of performing screens in silico can be faster and less expensive than HTS methods, virtual screening methods may provide the key to limit the number of compounds to be evaluated by HTS to a subset of molecules that are more likely to yield “hits” when screened. For the practical advantages of virtual screening to be realized, computational methods must excel in speed, economy, and accuracy. Striking the right balance of these criteria …