title: Molecular origins of internal friction effects on protein-folding rates.
abstract: Recent experiments on protein-folding dynamics have revealed strong evidence for internal friction effects. That is, observed relaxation times are not simply proportional to the solvent viscosity as might be expected if the solvent were the only source of friction. However, a molecular interpretation of this remarkable phenomenon is currently lacking. Here, we use all-atom simulations of peptide and protein folding in explicit solvent, to probe the origin of the unusual viscosity dependence. We find that an important contribution to this effect, explaining the viscosity dependence of helix formation and the folding of a helix-containing protein, is the insensitivity of torsion angle isomerization to solvent friction. The influence of this landscape roughness can, in turn, be quantitatively explained by a rate theory including memory friction. This insensitivity of local barrier crossing to solvent friction is expected to contribute to the viscosity dependence of folding rates in larger proteins.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: David
authors.initials: D
authors.lastname: de Sancho
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Anshul
authors.initials: A
authors.lastname: Sirur
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Best
mesh_terms: D017276:Friction; D056004:Molecular Dynamics Simulation; D017510:Protein Folding; D014783:Viscosity