On the role of chemical detail in simulating protein folding kinetics

Abstract

Is an all-atom representation for protein and solvent necessary for simulating protein folding kinetics or can simpler models reproduce the results of more complex models? This question is relevant not just for simulation methodology, but also for the general understanding of the chemical details relevant for protein dynamics. With recent advances in computational methodology.. it is now possible to simulate the folding kinetics of small proteins in all-atom detail. Therefore, with both detailed and simplified models of folding in hand, the outstanding questions are what the differences in these models are for the description of protein folding dynamics, and how we can quantitatively compare the folding mechanisms found in the models. To address the outstanding problem of how to determine the differences between folding mechanism in a sensitive and quantitative manner, we suggest a new method to quantify the non-linear correlation in folding commitment probability (P-fold) values. We use this method to probe the differences between a wide range of models for folding simulations, ranging from coarse grained Go models to all-atom models with implicit or explicit solvation. While the differences between less-detailed models (Go and implicit solvation models) and explicit solvation models are large, the differences within various explicit solvation models appear to be small, suggesting that the discrete nature of water may play a role in folding kinetics. (c) 2005 Elsevier B.V. All rights reserved.