Folding of proteins with an all-atom Ḡ-model

Abstract

The Ḡ-like potential at a residual level has been successfully applied to the folding of proteins in many previous works. However, taking into consideration more detailed structural information in the atomic level, the definition of contacts used in these traditional G-models may not be suitable for all-atom simulations. Here, in this work, we develop a rational definition of contacts considering the screening effect in the crowded intramolecular environment. In such a scheme, a large amount of screened atom pairs are excluded and the number of contacts is decreased compared to the case of the traditional definition. These contacts defined by such a new definition are compatible with the all-atom representation of protein structures. To verify the rationality of the new definition of contacts, the folding of proteins CI2 and SH3 is simulated by all-atom molecular dynamics simulations. A high folding cooperativity and good correlation of the simulated -values with those obtained experimentally, especially for CI2, are found. This suggests that the all-atom G-model is improved compared to the traditional G-model. Based on the comparison of the -values, the roles of side chains in the folding are discussed, and it is concluded that the side-chain structures are more important for local contacts in determining the transition state structures. Moreover, the relations between side chain and backbone orderings are also discussed. © 2008 American Institute of Physics.