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Science 10 April 2009:
Vol. 324. no. 5924, pp. 213 - 215
DOI: 10.1126/science.1169378
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Perspective

Trapping Moving Targets with Small Molecules

Gregory M. Lee and Charles S. Craik*

Structure-based drug design traditionally uses static protein models as inspirations for focusing on "active" site targets. Allosteric regulation of biological macromolecules, however, is affected by both conformational and dynamic properties of the protein or protein complex and can potentially lead to more avenues for therapeutic development. We discuss the advantages of searching for molecules that conformationally trap a macromolecule in its inactive state. Although multiple methodologies exist to probe protein dynamics and ligand binding, our current discussion highlights the use of nuclear magnetic resonance spectroscopy in the drug discovery and design process.

Department of Pharmaceutical Chemistry, University of California, San Francisco (UCSF), 600 16th Street, Box 2280, San Francisco, CA 94158–2280, USA.

* To whom correspondence should be addressed. E-mail: craik{at}cgl.ucsf.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Update of TTD: Therapeutic Target Database.
F. Zhu, B. Han, P. Kumar, X. Liu, X. Ma, X. Wei, L. Huang, Y. Guo, L. Han, C. Zheng, et al. (2009)
Nucleic Acids Res.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)