title: Peptide chain dynamics in light and heavy water: zooming in on internal friction.
abstract: Frictional effects due to the chain itself, rather than the solvent, may have a significant effect on protein dynamics. Experimentally, such "internal friction" has been investigated by studying folding or binding kinetics at varying solvent viscosity; however, the molecular origin of these effects is hard to pinpoint. We consider the kinetics of disordered glycine-serine and α-helix forming alanine peptides and a coarse-grained protein folding model in explicit-solvent molecular dynamics simulations. By varying the solvent mass over more than two orders of magnitude, we alter only the solvent viscosity and not the folding free energy. Folding dynamics at the near-vanishing solvent viscosities accessible by this approach suggests that solvent and internal friction effects are intrinsically entangled. This finding is rationalized by calculation of the polymer end-to-end distance dynamics from a Rouse model that includes internal friction. An analysis of the friction profile along different reaction coordinates, extracted from the simulation data, demonstrates that internal as well as solvent friction varies substantially along the folding pathways and furthermore suggests a connection between friction and the formation of hydrogen bonds upon folding.
authors.affiliation: Fachbereich Physik, Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: Julius C F
authors.initials: JC
authors.lastname: Schulz
authors.forename: Lennart
authors.initials: L
authors.lastname: Schmidt
authors.forename: Robert B
authors.initials: RB
authors.lastname: Best
authors.forename: Joachim
authors.initials: J
authors.lastname: Dzubiella
authors.forename: Roland R
authors.initials: RR
authors.lastname: Netz
mesh_terms: D002627:Chemistry, Physical / Q000379:methods; D003198:Computer Simulation; D017666:Deuterium Oxide / Q000737:chemistry*; D017276:Friction; D006860:Hydrogen Bonding; D007700:Kinetics; D008956:Models, Chemical; D015233:Models, Statistical; D016011:Normal Distribution; D010455:Peptides / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D014783:Viscosity; D014867:Water / Q000737:chemistry*
chemical_list: D010455:Peptides; D011108:Polymers; D012997:Solvents; D014867:Water; D017666:Deuterium Oxide