Year: 2014
Type: article
Abstract: A detailed understanding of temperature and pressure effects on an infinitely dilute protein's conformational equilibrium requires knowledge of the corresponding infinitely dilute partial molar properties. Established molecular dynamics methodologies generally have not provided a way to calculate these properties without either a loss of thermodynamic rigor, the introduction of nonunique parameters, or a loss of information about which solute conformations specifically contributed to the output values. Here we implement a simple method that is thermodynamically rigorous and possesses none of the above disadvantages, and we report on the method's feasibility and computational demands. We calculate infinitely dilute partial molar properties for two proteins and attempt to distinguish the thermodynamic differences between a native and a denatured conformation of a designed miniprotein. We conclude that simple ensemble average properties can be calculated with very reasonable amounts of computational power. In contrast, properties corresponding to fluctuating quantities are computationally demanding to calculate precisely, although they can be obtained more easily by following the temperature and/or pressure dependence of the corresponding ensemble averages.
DOI: 10.1021/jp508632h
Authors: Elizabeth A. Ploetz, Paul E. Smith
Institution: Kansas State University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W2320485711