title: Infinitely dilute partial molar properties of proteins from computer simulation.
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.
authors.affiliation: Department of Chemistry, Kansas State University , 213 CBC Building, Manhattan, Kansas 66506-0401, United States.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ploetz
authors.forename: Paul E
authors.initials: PE
authors.lastname: Smith
mesh_terms: D056004:Molecular Dynamics Simulation; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D011489:Protein Denaturation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D011506:Proteins; D014867:Water; D009113:Muramidase