期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：46
页码：17754-17759
DOI：10.1073/pnas.0804775105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 {Delta}Gu(P,T) landscape using the simulation data and propose a stablility 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 {Delta}Eu are roughly linearly temperature-dependent and approach {Delta}Eu = 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.
关键词：folding ; free energy ; hydrostatic pressure ; simulations
