Computing the Amino Acid Specificity of Fluctuations in Biomolecular Systems

• Published in: Journal of chemical theory and computation Vol. 2; no. 3; pp. 873 - 878
• Main Authors: Hamacher, K, McCammon, J. A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.05.2006
• ISSN: 1549-9618; 1549-9626
• DOI: 10.1021/ct050247s

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.