Kinetics of α-helix formation as diffusion on a one-dimensional free energy surface

A question of great interest is whether Kramers-rate theory can be used to describe the highly complex conformational dynamics of biopolymers. In this paper we investigate this question in the context of the kinetics of the helix-coil transition. The formation of alpha-helices is possibly the dynamic process related to protein folding for which there is a better mechanistic understanding. Using a master equation-based model of the helix-coil transition we calculate the relaxation kinetics of alpha-helix forming peptides after perturbations induced by 'instantaneous' jumps in temperature. These calculations successfully simulate the results of recent laser-induced temperature-jump experiments. We compare the time courses generated by such detailed model with the relaxation kinetics obtained by diffusion on a one-dimensional free energy surface derived from the projection of the free energy of the helix-coil transition onto the order parameter H (i.e., number of helical peptide bonds). The diffusive kinetics calculated with a constant effective diffusion coefficient of similar to0.6 x 10(9) pb(2) s(-1) are in very good agreement with the results of the detailed kinetic model, indicating that H is an appropriate reaction coordinate for alpha-helix formation. (C) 2004 Elsevier B.V. All rights reserved.