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Electrostatics of Hydrogen Exchange for Analyzing Protein Flexibility

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Protein NMR Techniques

Part of the book series: Methods in Molecular Biology ((MIMB,volume 831))

Abstract

Electrostatic interactions at the protein–aqueous interface modulate the reactivity of solvent-exposed backbone amides by a factor of at least a billion fold. The brief (∼10 ps) lifetime of the peptide anion formed during the hydroxide-catalyzed exchange reaction helps enable the experimental rates to be robustly predictable by continuum dielectric methods. Since this ability to predict the structural dependence of exchange reactivity also applies to the protein amide hydrogens that are only rarely exposed to the bulk solvent phase, electrostatic analysis of the experimental exchange rates provides an effective assessment of whether a given model ensemble is consistent with the properly weighted Boltzmann conformational distribution of the protein native state.

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Authors and Affiliations

  1. Department of Health and Department of Biomedical Sciences, Wadsworth Center, School of Public Health, University at Albany – SUNY, Albany, NY, USA

    Griselda Hernández & David M. LeMaster

  2. Department of Chemistry, Union College, Schenectady, NY, USA

    Janet S. Anderson

Authors
  1. Griselda Hernández
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  2. Janet S. Anderson
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  3. David M. LeMaster
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Corresponding author

Correspondence to David M. LeMaster .

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Editors and Affiliations

  1. University of Albany, State University of New York, Washington Avenue 1400, Albany, 12222, New York, USA

    Alexander Shekhtman

  2. University of Albany, State University of New York, Washington Avenue 1400, Albany, 12222, New York, USA

    David S. Burz

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Hernández, G., Anderson, J.S., LeMaster, D.M. (2012). Electrostatics of Hydrogen Exchange for Analyzing Protein Flexibility. In: Shekhtman, A., Burz, D. (eds) Protein NMR Techniques. Methods in Molecular Biology, vol 831. Humana Press. https://doi.org/10.1007/978-1-61779-480-3_20

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  • DOI: https://doi.org/10.1007/978-1-61779-480-3_20

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-479-7

  • Online ISBN: 978-1-61779-480-3

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