Prediction of protein conformational freedom from distance constraints

Authors

  • B.L. de Groot,

    1. Groningen Biomolecular Sciences and Biotechnology Institute (GBB), Department of Biophysical Chemistry, University of Groningen, Groningen, The Netherlands
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  • D.M.F. van Aalten,

    1. Keck Structural Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York
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  • R.M. Scheek,

    1. Groningen Biomolecular Sciences and Biotechnology Institute (GBB), Department of Biophysical Chemistry, University of Groningen, Groningen, The Netherlands
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  • A. Amadei,

    1. Groningen Biomolecular Sciences and Biotechnology Institute (GBB), Department of Biophysical Chemistry, University of Groningen, Groningen, The Netherlands
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  • G. Vriend,

    1. EMBL, Heidelberg, Germany
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  • H.J.C. Berendsen

    Corresponding author
    1. Groningen Biomolecular Sciences and Biotechnology Institute (GBB), Department of Biophysical Chemistry, University of Groningen, Groningen, The Netherlands
    • Groningen Biomolecular Sciences and Biotechnology Institute, Department of Biophysical Chemistry, University of Groningen, Nyenborgh 4, 9747 AG, Groningen, The Netherlands
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Abstract

A method is presented that generates random protein structures that fulfil a set of upper and lower interatomic distance limits. These limits depend on distances measured in experimental structures and the strength of the interatomic interaction. Structural differences between generated structures are similar to those obtained from experiment and from MD simulation. Although detailed aspects of dynamical mechanisms are not covered and the extent of variations are only estimated in a relative sense, applications to an IgG-binding domain, an SH3 binding domain, HPr, calmodulin, and lysozyme are presented which illustrate the use of the method as a fast and simple way to predict structural variability in proteins. The method may be used to support the design of mutants, when structural fluctuations for a large number of mutants are to be screened. The results suggest that motional freedom in proteins is ruled largely by a set of simple geometric constraints. Proteins 29:240–251, 1997. © 1997 Wiley-Liss, Inc.

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