pK(a) shift effects on backbone amide base-catalyzed hydrogen exchange rates in peptides

Federico Fogolari, Gennaro Esposito, Paolo Viglino, James M. Briggs, J. Andrew McCammon

    Research output: Contribution to journalArticle

    Abstract

    Amide proton exchange (HX) rates are known to depend on protein primary structure as well as local and global protein structure and dynamics. Measurement of HX rates gives information on the local exposure of amide protons to solvent and on local rates of structural openings. It has long been recognized that the amide pK(a) directly influences the HX rate. Using the finite-difference solution of the Poisson-Boltzmann equation, we investigated the electrostatic effects on HX rates, via calculated shifts in the amide pK(a) for model compounds (N-methylacetamide, dipeptides entailing almost all amino acid side chains, and a tripeptide). Rather than shifts in the same compound with varying environmental conditions, we address shifts in the HX rates of different compounds relative to each other. The results for selected model compounds which resemble Ala and Gly residues, with a standard choice of parameters, agree to a high degree of accuracy with experimentally determined rates. Application of the same methodology to naturally occurring amino acids is promising but requires refinement to take into account flexibility and inductive effects.

    Original languageEnglish (US)
    Pages (from-to)3735-3738
    Number of pages4
    JournalJournal of the American Chemical Society
    Volume120
    Issue number15
    DOIs
    StatePublished - Apr 22 1998

    Fingerprint

    Amides
    Peptides
    Hydrogen
    Ion exchange
    Protons
    Amino acids
    Proteins
    Amino Acids
    Boltzmann equation
    Dipeptides
    Static Electricity
    Amino Acid Sequence
    Electrostatics

    ASJC Scopus subject areas

    • Catalysis
    • Chemistry(all)
    • Biochemistry
    • Colloid and Surface Chemistry

    Cite this

    pK(a) shift effects on backbone amide base-catalyzed hydrogen exchange rates in peptides. / Fogolari, Federico; Esposito, Gennaro; Viglino, Paolo; Briggs, James M.; McCammon, J. Andrew.

    In: Journal of the American Chemical Society, Vol. 120, No. 15, 22.04.1998, p. 3735-3738.

    Research output: Contribution to journalArticle

    Fogolari, F, Esposito, G, Viglino, P, Briggs, JM & McCammon, JA 1998, 'pK(a) shift effects on backbone amide base-catalyzed hydrogen exchange rates in peptides', Journal of the American Chemical Society, vol. 120, no. 15, pp. 3735-3738. https://doi.org/10.1021/ja963133m
    Fogolari, Federico ; Esposito, Gennaro ; Viglino, Paolo ; Briggs, James M. ; McCammon, J. Andrew. / pK(a) shift effects on backbone amide base-catalyzed hydrogen exchange rates in peptides. In: Journal of the American Chemical Society. 1998 ; Vol. 120, No. 15. pp. 3735-3738.
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    AU - Fogolari, Federico

    AU - Esposito, Gennaro

    AU - Viglino, Paolo

    AU - Briggs, James M.

    AU - McCammon, J. Andrew

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