• Open Access

Measuring the successes and deficiencies of constant pH molecular dynamics: A blind prediction study

Authors

  • Sarah L. Williams,

    Corresponding author
    1. Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, California 92093-0365
    • Department of Chemistry & Biochemistry, University of California, San Diego, 9500 Gilman Drive, Mail code 0365, La Jolla, CA 92093-0365
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    • Sarah L. Williams and Patrick G. Blachly contributed equally to this work.

  • Patrick G. Blachly,

    1. Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, California 92093-0365
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    • Sarah L. Williams and Patrick G. Blachly contributed equally to this work.

  • J. Andrew McCammon

    1. Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, California 92093-0365
    2. Center for Theoretical Biological Physics, University of California San Diego, La Jolla, California 92093
    3. Howard Hughes Medical Institute, University of California San Diego, La Jolla, California 92093-0365
    4. Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0365
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  • The authors state no conflict of interest.

Abstract

A constant pH molecular dynamics method has been used in the blind prediction of pKa values of titratable residues in wild type and mutated structures of the Staphylococcal nuclease (SNase) protein. The predicted values have been subsequently compared to experimental values provided by the laboratory of García-Moreno. CpHMD performs well in predicting the pKa of solvent-exposed residues. For residues in the protein interior, the CpHMD method encounters some difficulties in reaching convergence and predicting the pKa values for residues having strong interactions with neighboring residues. These results show the need to accurately and sufficiently sample conformational space in order to obtain pKa values consistent with experimental results. Proteins 2011; © 2011 Wiley-Liss, Inc.

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