title: Computing the stability diagram of the Trp-cage miniprotein.
abstract: We report molecular dynamics simulations of the equilibrium folding/unfolding thermodynamics of an all-atom model of the Trp-cage miniprotein in explicit solvent. Simulations are used to sample the folding/unfolding free energy difference and its derivatives along 2 isochores. We model the DeltaG(u)(P,T) landscape using the simulation data and propose a stability diagram model for Trp-cage. We find the proposed diagram to exhibit features similar to globular proteins with increasing hydrostatic pressure destabilizing the native fold. The observed energy differences DeltaE(u) are roughly linearly temperature-dependent and approach DeltaE(u) = 0 with decreasing temperature, suggesting that the system approached the region of cold denaturation. In the low-temperature denatured state, the native helical secondary structure elements are largely preserved, whereas the protein conformation changes to an "open-clamp" configuration. A tighter packing of water around nonpolar sites, accompanied by an increasing solvent-accessible surface area of the unfolded ensemble, seems to stabilize the unfolded state at elevated pressures.
authors.affiliation: Fakultät Bio- und Chemieingenieurwesen, Emil-Figge-Strasse 70, Technische Universität Dortmund, D-44227 Dortmund, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Paschek
authors.forename: Sascha
authors.initials: S
authors.lastname: Hempel
authors.forename: Angel E
authors.initials: AE
authors.lastname: García
mesh_terms: D003198:Computer Simulation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D010455:Peptides; C508725:Trp-cage peptide; D014867:Water