title: Rate constant and reaction coordinate of Trp-cage folding in explicit water.
abstract: We report rate constant calculations and a reaction coordinate analysis of the rate-limiting folding and unfolding process of the Trp-cage mini-protein in explicit solvent using transition interface sampling. Previous transition path sampling simulations revealed that in this (un)folding process the protein maintains its compact configuration, while a (de)increase of secondary structure is observed. The calculated folding rate agrees reasonably with experiment, while the unfolding rate is 10 times higher. We discuss possible origins for this mismatch. We recomputed the rates with the forward flux sampling method, and found a discrepancy of four orders of magnitude, probably caused by the method's higher sensitivity to the choice of order parameter with respect to transition interface sampling. Finally, we used the previously computed transition path-sampling ensemble to screen combinations of many order parameters for the best model of the reaction coordinate by employing likelihood maximization. We found that a combination of the root mean-square deviation of the helix and of the entire protein was, of the set of tried order parameters, the one that best describes the reaction coordination.
authors.affiliation: van' t Hoff institute for Molecular Science, Universiteit van Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jarek
authors.initials: J
authors.lastname: Juraszek
authors.forename: Peter G
authors.initials: PG
authors.lastname: Bolhuis
mesh_terms: D000595:Amino Acid Sequence; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry*
chemical_list: D010455:Peptides; D012997:Solvents; C508725:Trp-cage peptide; D014867:Water