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Prediction of new serine proteinase inhibitors

Nature Structural Biology volume 1, pages 735–743 (1994)Cite this article

Abstract

We describe here the use of a rapid computational method to predict the relative binding strengths of a series of small-molecule ligands for the serine proteinase trypsin. Flexible molecular models of the ligands were docked to the proteinase using an all-atom potential set, without cutoff limits for the non-bonded and electrostatic energies. The binding-strength calculation is done directly in terms of a molecular mechanics potential. The binding of eighteen different compounds, including non-binding controls, has been successfully predicted. The measured Ki is correlated with the predicted energy. The correctness of the theoretical calculations is demonstrated with both kinetics measurements and X-ray structure determination of six enzyme-inhibitor complexes.

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Authors and Affiliations

  1. Department of Pharmacology, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA, 19107, U.S.A.

    I.V. Kurinov & R.W. Harrison

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  1. I.V. Kurinov
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  2. R.W. Harrison
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Kurinov, I., Harrison, R. Prediction of new serine proteinase inhibitors. Nat Struct Mol Biol 1, 735–743 (1994). https://doi.org/10.1038/nsb1094-735

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