Banding 2of NMR-derived methyl order parameters: Implications for protein dynamics

Authors

  • Kim A. Sharp,

    Corresponding author
    1. Department of Biochemistry and Biophysics, Graduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
    2. Department of Biochemistry and Biophysics, Johnson Research Foundation, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
    • Correspondence to: A. J. Wand, Department of Biochemistry and Biophysics, University of Pennsylvania, 905 Stellar-Chance Laboratories, 422 Curie Blvd., Philadelphia, Pennsylvania 19104-6059. E-mail: wand@mail.med.upenn.edu or sharpk@mail.med.upenn.edu

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  • Vignesh Kasinath,

    1. Department of Biochemistry and Biophysics, Graduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
    2. Department of Biochemistry and Biophysics, Johnson Research Foundation, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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  • A. Joshua Wand

    Corresponding author
    1. Department of Biochemistry and Biophysics, Graduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
    2. Department of Biochemistry and Biophysics, Johnson Research Foundation, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
    • Correspondence to: A. J. Wand, Department of Biochemistry and Biophysics, University of Pennsylvania, 905 Stellar-Chance Laboratories, 422 Curie Blvd., Philadelphia, Pennsylvania 19104-6059. E-mail: wand@mail.med.upenn.edu or sharpk@mail.med.upenn.edu

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ABSTRACT

Our understanding of protein folding, stability, and function has begun to more explicitly incorporate dynamical aspects. Nuclear magnetic resonance has emerged as a powerful experimental method for obtaining comprehensive site-resolved insight into protein motion. It has been observed that methyl-group motion tends to cluster into three “classes” when expressed in terms of the popular Lipari-Szabo model-free squared generalized order parameter. Here the origins of the three classes or bands in the distribution of order parameters are examined. As a first step, a Bayesian based approach, which makes no a priori assumption about the existence or number of bands, is developed to detect the banding of math formula values derived either from NMR experiments or molecular dynamics simulations. The analysis is applied to seven proteins with extensive molecular dynamics simulations of these proteins in explicit water to examine the relationship between O2 and fine details of the motion of methyl bearing side chains. All of the proteins studied display banding, with some subtle differences. We propose a very simple yet plausible physical mechanism for banding. Finally, our Bayesian method is used to analyze the measured distributions of methyl group motions in the catabolite activating protein and several of its mutants in various liganded states and discuss the functional implications of the observed banding to protein dynamics and function. Proteins 2014; 82:2106–2117. © 2014 Wiley Periodicals, Inc.

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