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Molecular docking programs successfully predict the binding of a β-lactamase inhibitory protein to TEM-1 β-lactamase

Nature Structural Biology volume 3, pages 233–239 (1996)Cite this article

Abstract

Crystallization of the 1:1 molecular complex between the β-lactamase TEM-1 and the β-lactamase inhibitory protein BLIP has provided an opportunity to put a stringent test on current protein-docking algorithms. Prior to the successful determination of the structure of the complex, nine laboratory groups were given the refined atomic coordinates of each of the native molecules. Other than the fact that BLIP is an effective inhibitor of a number of β-lactamase enzymes (KI for TEM-1∼100 pM) no other biochemical or structural data were available to assist the practitioners in their molecular docking. In addition, it was not known whether the molecules underwent conf ormational changes upon association or whether the inhibition was competitive or non-competitive. All six of the groups that accepted the challenge correctly predicted the general mode of association of BLIP and TEM-1.

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Authors and Affiliations

  1. MRC Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada

    N.C.J. Strynadka & M.N.G. James

  2. Departments of Chemical Services & Membrane Research and Biochemistry, Weizmann Institute of Science, Rehovot, 76100, Israel

    M. Eisenstein & E. Katchalski-Katzir

  3. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois, 60611, USA

    B.K. Shoichet

  4. Department of Pharmaceutical Chemistry, UCSF, San Francisco, California, 94143-0446, USA

    I.D. Kuntz

  5. Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York, NY, 10016, USA

    R. Abagyan & M. Totrov

  6. Laboratoire de Biologie Structurale, UMR 9920 C.N.R.S., Université Paris-Sud, Bat. 34-1 Avenue de la Terrasse, 91198, Gif-sur-Yvette, France

    J. Janin, J. Cherfils & F. Zimmerman

  7. The Scripps Research Institute, MB-5,10666 North Torrey Pines Road, La Jolla, CA, 92037, USA

    A. Olson, B. Duncan & M. Rao

  8. Biomolecular Modelling Laboratory, Imperial Cancer Research Fund, P.O. Box 123, 44 Lincoln's Inn Fields, London, WC2A3PX, UK

    R. Jackson & M. Sternberg

Authors
  1. N.C.J. Strynadka
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  2. M. Eisenstein
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  6. R. Abagyan
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  8. J. Janin
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  9. J. Cherfils
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  10. F. Zimmerman
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  11. A. Olson
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  13. M. Rao
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  16. M.N.G. James
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Strynadka, N., Eisenstein, M., Katchalski-Katzir, E. et al. Molecular docking programs successfully predict the binding of a β-lactamase inhibitory protein to TEM-1 β-lactamase. Nat Struct Mol Biol 3, 233–239 (1996). https://doi.org/10.1038/nsb0396-233

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  • DOI: https://doi.org/10.1038/nsb0396-233

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