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Locating and characterizing binding sites on proteins

Nature Biotechnology volume 14, pages 595–599 (1996)Cite this article

Abstract

This review article begins with a discussion of fundamental differences between substrates and inhibitors, and some of the assumptions and goals underlying the design of a new ligand to a target protein. An overview is given of the methods currently used to locate and characterize ligand binding sites on protein surfaces, with focus on a novel approach: multiple solvent crystal structures (MSCS). In this method, the X-ray crystal structure of the target protein is solved in a variety of organic solvents. Each type of solvent molecule serves as a probe for complementary binding sites on the protein. The probe distribution on the protein surface allows the location of binding sites and the characterization of the potential ligand interactions within these sites. General aspects of the application of the MSCS method to porcine pancreatic elastase is discussed, and comparison of the results with those from X-ray crystal structures of elastase/inhibitor complexes is used to illustrate the potential of the method in aiding the process of rational drug design.

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Author notes

  1. Dagmar Ringe: e-mail: ringe@binah.cc.brandeis.edu.

Authors and Affiliations

  1. Rosenstiel Basic Medical Sciences Research Center, Brandeis Universiy, 415 South St., Waltham, MA, 02254

    Carla Mattos

Authors
  1. Carla Mattos
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  2. Dagmar Ringe
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Mattos, C., Ringe, D. Locating and characterizing binding sites on proteins. Nat Biotechnol 14, 595–599 (1996). https://doi.org/10.1038/nbt0596-595

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