Quantifying kinetic paths of protein folding

Abstract

We propose a new approach to activated protein folding dynamics via a diffusive path integral framework. The important issues of kinetic paths in this situation can be directly addressed. This leads to the identification of the kinetic paths of the activated folding process, and provides a direct tool and language for the theoretical and experimental community to understand the problem better. The kinetic paths giving the dominant contributions to the long-time folding activation dynamics can be quantitatively determined. These are shown to be the instanton paths. The contributions of these instanton paths to the kinetics lead to the "bell-like" shape folding rate dependence on temperature, which is in good agreement with folding kinetic experiments and simulations. The connections to other approaches as well as the experiments of the protein folding kinetics are discussed. © 2005 by the Biophysical Society.