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Article

Computing the Amino Acid Specificity of Fluctuations in Biomolecular Systems

K. Hamacher*^†^‡ and J. A. McCammon^†^‡^§

Center for Theoretical Biological Physics, Department of Chemistry and Biochemistry, Department of Pharmacology, and Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California 92093-0365

J. Chem. Theory Comput., 2006, 2 (3), pp 873–878

DOI: 10.1021/ct050247s

Publication Date (Web): April 15, 2006

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

†

Center for Theoretical Biological Physics.

‡

Department of Chemistry and Biochemistry.

Department of Pharmacology and Howard Hughes Medical Institute.

Abstract

We developed a new amino acid specific method for the computation of spatial fluctuations of proteins around their native structures. We show the consistency with experimental values and the increased performance in comparison to an established model, based on statistical estimates for a set of test proteins. We apply the new method to HIV-1 protease in its wild-type form and to a V82F−I84V mutant that shows resistance to protease inhibitors. We further show how the method can be successfully used to explain the molecular biophysics of drug resistance of the mutant.

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