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Virtual screening of chemical libraries

Nature volume 432, pages 862–865 (2004)Cite this article

Abstract

Virtual screening uses computer-based methods to discover new ligands on the basis of biological structures. Although widely heralded in the 1970s and 1980s, the technique has since struggled to meet its initial promise, and drug discovery remains dominated by empirical screening. Recent successes in predicting new ligands and their receptor-bound structures, and better rates of ligand discovery compared to empirical screening, have re-ignited interest in virtual screening, which is now widely used in drug discovery, albeit on a more limited scale than empirical screening.

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Figure 1: Complexes predicted from virtual screening compared to X-ray crystallographic structures that were subsequently determined.
Figure 2: Virtual screening for new ligands.
Figure 3: Comparing the structures of new ligands predicted from virtual screening to the structures subsequently determined experimentally.

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Acknowledgements

I thank G. Klebe, A. Olson, and W. Jorgensen for contributing figures and comments, and I. D. Kuntz, M. Jacobson, A. Sali, K. Dill and J. Irwin for many insightful conversations. My laboratory's research in docking is supported by NIGMS.

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  1. Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, 94143-2240, California, USA

    Brian K. Shoichet

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Competing interests

B. Shoichet is a partner in a company, Blue Dolphin LLC, that conducts inhibitor discovery campaigns for pharmaceutical and biotech companies.

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Shoichet, B. Virtual screening of chemical libraries. Nature 432, 862–865 (2004). https://doi.org/10.1038/nature03197

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