Table of Contents

Article

Recovering Kinetics from a Simplified Protein Folding Model Using Replica Exchange Simulations: A Kinetic Network and Effective Stochastic Dynamics

Weihua Zheng^†, Michael Andrec^‡, Emilio Gallicchio^‡ and Ronald M. Levy*^‡

Department of Physics and Astronomy, Rutgers, The State University of New Jersey, 136 Frelinghuysen Road, Piscataway, New Jersey 08854, and Department of Chemistry and Chemical Biology and BioMaPS Institute for Quantitative Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey 08854

J. Phys. Chem. B, 2009, 113 (34), pp 11702–11709

DOI: 10.1021/jp900445t

Publication Date (Web): August 5, 2009

* To whom correspondence should be addressed. E-mail: ronlevy@lutece.rutgers.edu. Phone: 732-445-3947. Fax: 732-445-5958., †

Department of Physics and Astronomy.

, ‡

Department of Chemistry and Chemical Biology and BioMaPS Institute for Quantitative Biology.

Abstract

We present an approach to recover kinetics from a simplified protein folding model at different temperatures using the combined power of replica exchange (RE), a kinetic network, and effective stochastic dynamics. While RE simulations generate a large set of discrete states with the correct thermodynamics, kinetic information is lost due to the random exchange of temperatures. We show how we can recover the kinetics of a 2D continuous potential with an entropic barrier by using RE-generated discrete states as nodes of a kinetic network. By choosing the neighbors and the microscopic rates between the neighbors appropriately, the correct kinetics of the system can be recovered by running a kinetic simulation on the network. We fine-tune the parameters of the network by comparison with the effective drift velocities and diffusion coefficients of the system determined from short-time stochastic trajectories. One of the advantages of the kinetic network model is that the network can be built on a high-dimensional discretized state space, which can consist of multiple paths not consistent with a single reaction coordinate.