TY - DATA T1 - Comparing Fast Pressure Jump and Temperature Jump Protein Folding Experiments and Simulations PY - 2015/06/10 AU - Anna Jean Wirth AU - Yanxin Liu AU - Maxim B. Prigozhin AU - Klaus Schulten AU - Martin Gruebele UR - https://acs.figshare.com/articles/media/Comparing_Fast_Pressure_Jump_and_Temperature_Jump_Protein_Folding_Experiments_and_Simulations/2159296 DO - 10.1021/jacs.5b02474.s006 L4 - https://ndownloader.figshare.com/files/3793183 KW - Temperature Jump Protein KW - FiP KW - MD KW - pressure jump KW - pressure jump experiments KW - WW KW - Fast Pressure Jump KW - pressure jump simulations KW - phase KW - temperature jump refolding kinetics N2 - The unimolecular folding reaction of small proteins is now amenable to a very direct mechanistic comparison between experiment and simulation. We present such a comparison of microsecond pressure and temperature jump refolding kinetics of the engineered WW domain FiP35, a model system for β-sheet folding. Both perturbations produce experimentally a faster and a slower kinetic phase, and the “slow” microsecond phase is activated. The fast phase shows differences between perturbation methods and is closer to the downhill limit by temperature jump, but closer to the transiently populated intermediate limit by pressure jump. These observations make more demands on simulations of the folding process than just a rough comparison of time scales. To complement experiments, we carried out several pressure jump and temperature jump all-atom molecular dynamics trajectories in explicit solvent, where FiP35 folded in five of the six simulations. We analyzed our pressure jump simulations by kinetic modeling and found that the pressure jump experiments and MD simulations are most consistent with a 4-state kinetic mechanism. Together, our experimental and computational data highlight FiP35’s position at the boundary where activated intermediates and downhill folding meet, and we show that this model protein is an excellent candidate for further pressure jump molecular dynamics studies to compare experiment and modeling at the folding mechanism level. ER -