Successful Applications of Virtual Screening

The fourth and most complex step requires even more structural knowledge when potential candidate molecules are flexibly docked into binding sites of target protein structures and candidates for biological testing are then selected using scoring functions. 

Although an increasing number of prospective virtual screening outcomes are now reported, most studies are still retrospective with a focus on novel software or virtual 

The first section provides an overview of successful structure-based virtual screening applications, followed by some comments on structure-based library design. This is followed by a summary of recent ligand-based virtual screening examples. Within each section, examples are organized by target families to focus on successes and challenges in different areas relevant to medicinal chemistry. 

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Virtual screening is not a replacement for experimental HTS and is perhaps best viewed as an aid to HTS. Using virtual screening as a prefilter can allow one to select subsets of compounds (focused library) from a larger library and reduces the cost and time required for subsequent experimental screening. Several success stories of virtual screening applications (73) demonstrate the utility of these computational methods for drug discovery, both in academia and industry. 

Fig. 4.5 Examples of successful virtual screening approaches. All structures (a-l) are active against different target proteins or receptors, they were discovered in prospective applications using a variety of virtual screening approaches and work flows. See text for details.

The following table provides a brief compilation of virtual screening application studies mentioned in the chapters of this book. Additional case studies not mentioned in the book are taken from the following review and are denoted with ( ) H. Kubinyi, Success Stories of Computer-Aided Design, in Computer Applications in Pharmaceutical Research and Development, edited by Sean Ekins, John Wiley Sons, Inc., 2006. 

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