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Drug discovery

Pulled from a protein's embrace

Nature volume 466, pages 42–43 (2010)Cite this article

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It is hard to predict how strongly a small molecule will bind to a protein, but this is a crucial goal of computer-aided drug discovery. A new approach models the forcible removal of molecules from a protein's active site.

Most drugs are small ligand molecules that bind to a protein. Some disrupt protein–protein interactions, whereas many others — enzyme inhibitors — inhibit reactions carried out by proteins. Computational methods for accurately predicting the binding affinity of a ligand for a protein are therefore central to rational drug design. Reporting in the Journal of the American Chemical Society, Colizzi et al.1 describe a stimulating advance in this field: a computational method for predicting protein–ligand binding affinities that works by modelling the force that is required to pull inhibitors out of their complexes with proteins.

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Figure 1: Pulling simulations.

References

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  1. William L. Jorgensen is in the Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA. william.jorgensen@yale.edu,

    William L. Jorgensen

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  1. William L. Jorgensen
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Jorgensen, W. Pulled from a protein's embrace. Nature 466, 42–43 (2010). https://doi.org/10.1038/466042a

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