Viscosity Scaling for the Glassy Phase of Protein Folding

Although commendable progress has been made in the understanding of the physics of protein folding, a key unresolved issue is whether Kramers’ diffusion model of chemical reactions is generally applicable to activated barrier crossing events during folding. To examine the solvent viscosity effect on the folding transition of native-like trapped intermediates, laser flash photolysis has been used to measure the microsecond folding kinetics of a natively folded state of CO-liganded ferrocytochrome c (M-state) in the 1−250 cP range of glycerol viscosity at pH 7.0, 20 °C. The single rate coefficient for the folding of the M-state to the native state of the protein (i.e., the M → N folding process) decreases initially when the solvent viscosity is low (<10 cP), but saturates at higher viscosity, indicating that Kramers model is not general enough for scaling the viscosity dependence of post-transition folding involving glassy dynamics. Analysis based on the Grote−Hynes idea of time dependent friction in conjun...