title: Folding Thermodynamics and Mechanism of Five Trp-Cage Variants from Replica-Exchange MD Simulations with RSFF2 Force Field.
abstract: To test whether our recently developed residue-specific force field RSFF2 can reproduce the mutational effect on the thermal stability of Trp-cage mini-protein and decipher its detailed folding mechanism, we carried out long-time replica-exchange molecular dynamics (REMD) simulations on five Trp-cage variants, including TC5b and TC10b. Initiated from their unfolded structures, the simulations not only well-reproduce their experimental structures but also their melting temperatures and folding enthalpies reasonably well. For each Trp-cage variant, the overall folding free energy landscape is apparently two-state, but some intermediate states can be observed when projected on more detailed coordinates. We also found different variants have the same major folding pathway, including the well formed PII-helix in the unfolded state, the formation of W6-P12/P18/P19 contacts and the α-helix before the transition state, the following formation of most native contacts, and the final native loop formation. The folding mechanism derived here is consistent with many previous simulations and experiments.
authors.affiliation: Laboratory of Computational Chemistry and Drug Design, Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School , Shenzhen 518055, China.|College of Chemistry and Molecular Engineering, Peking University , Beijing 100871, China.
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Zhou
authors.affiliation: Laboratory of Computational Chemistry and Drug Design, Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School , Shenzhen 518055, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Laboratory of Computational Chemistry and Drug Design, Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School , Shenzhen 518055, China.|College of Chemistry and Molecular Engineering, Peking University , Beijing 100871, China.
authors.forename: Yun-Dong
authors.initials: YD
authors.lastname: Wu
mesh_terms: D007700:Kinetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D055550:Protein Stability; D013816:Thermodynamics
chemical_list: D010455:Peptides; C508725:Trp-cage peptide