From in Silico to in Vitro Drug Discovery

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Science  21 Apr 2006:
Vol. 312, Issue 5772, pp. 333
DOI: 10.1126/science.312.5772.333k

Many currently available therapeutic drugs act by modulating signaling through G protein (heterotrimeric GTP-binding protein)-coupled receptors. The G-protein βγ subunit transmits signals from G protein-coupled receptors to their targets, and many crystal structures of such complexes have been solved. Bonacci et al. (p. 443; see the Perspective by Tesmer) used a computer program to predict which chemical compounds would bind to the interaction site on the βγ subunits and obtained potent small molecule inhibitors of protein-protein interactions. Furthermore, these molecules showed specificity for disrupting signaling-specific downstream targets, which suggests that such reagents might be both effective and relatively free of side effects.

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