BIOPHYSICAL THEORY AND MODELING |
Predicting the folding pathway of engrailed homeodomain with a probabilistic roadmap enhanced reaction-path algorithm
Da-wei Li 1, Haijun Yang 1, Li Han 1 and Shuanghong Huo 1*
1 Clark University
* To whom correspondence should be addressed. E-mail: shuo{at}clarku.edu.
Submitted on August 6, 2007
Revised on September 13, 2007
Accepted on 31 October 2007
 |
Abstract |
|---|
To predict protein folding pathway, we present an alternative to the time consuming dynamical simulation of atomistic models. We replace the actual dynamical simulation with variational optimization of a reaction path connecting known initial and final protein conformations in such a way to maximize an estimate of the reactive flux or minimize the mean first passage time at a given temperature, referred to MaxFlux. We solve the MaxFlux global optimization problem with an efficient graph-theoretic approach, the probabilistic roadmap method (PRM). We employed CHARMM19 and EEF1 implicit solvation model to describe the protein solution. The effectiveness of our MaxFlux-PRM is demonstrated in our promising simulation results on the folding pathway of engrailed homeodomain. Our MaxFlux-PRM approach provides the direct evidence to support that the previously reported intermediate state is a genuine on-pathway intermediate, while the demand of CPU power is moderate.
Key Words:
CHARMM, engrailed domeodomain, intermediate state, probabilistic roadmap, protein folding pathway, reaction path
