title: Water Mediated Interactions and the Protein Folding Phase Diagram in the Temperature-Pressure Plane.
abstract: The temperature-pressure behavior of two proteins, ubiquitin and λ-repressor, is explored using a realistically coarse-grained physicochemical model, the associative memory, water mediated, structure and energy model (AWSEM). The phase diagram across the temperature-pressure plane is obtained by perturbing the water mediated interactions in the Hamiltonian systematically. The phase diagrams calculated with direct simulations along with an extended bridge sampling estimator show the main features found experimentally, including both cold- and pressure-denaturation. The denatured ensembles in different parts of the phase diagram are characterized and found to be structurally distinct. The protein energy landscape is found to be funneled throughout the phase diagram, but modest changes in the entropy and free energy of the water are found to drive both cold and pressure induced denaturation.
authors.affiliation: Center for Theoretical Biological Physics, Rice University , 6500 Main Street, Houston, Texas 77030, United States.|Department of Chemistry, Rice University , Space Science 201, Houston, Texas 77251, United States.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Sirovetz
authors.affiliation: Center for Theoretical Biological Physics, Rice University , 6500 Main Street, Houston, Texas 77030, United States.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Schafer
authors.affiliation: Center for Theoretical Biological Physics, Rice University , 6500 Main Street, Houston, Texas 77030, United States.|Department of Chemistry, Rice University , Space Science 201, Houston, Texas 77251, United States.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Wolynes
mesh_terms: D008958:Models, Molecular; D011312:Pressure; D017510:Protein Folding; D055550:Protein Stability; D012097:Repressor Proteins / Q000737:chemistry*; D013696:Temperature; D025801:Ubiquitin / Q000737:chemistry*; D014867:Water / Q000737:chemistry / Q000378:metabolism*
chemical_list: D012097:Repressor Proteins; D025801:Ubiquitin; D014867:Water