title: Computational model for protein unfolding simulation.
abstract: The protein folding problem is one of the fundamental and important questions in molecular biology. However, the all-atom molecular dynamics studies of protein folding and unfolding are still computationally expensive and severely limited by the time scale of simulation. In this paper, a simple and fast protein unfolding method is proposed based on the conformational stability analyses and structure modeling. In this method, two structure-based conditions are considered to identify the unstable regions of proteins during the unfolding processes. The protein unfolding trajectories are mimicked through iterative structure modeling according to conformational stability analyses. Two proteins, chymotrypsin inhibitor 2 (CI2) and α -spectrin SH3 domain (SH3) were simulated by this method. Their unfolding pathways are consistent with the previous molecular dynamics simulations. Furthermore, the transition states of the two proteins were identified in unfolding processes and the theoretical Φ values of these transition states showed significant correlations with the experimental data (the correlation coefficients are >0.8). The results indicate that this method is effective in studying protein unfolding. Moreover, we analyzed and discussed the influence of parameters on the unfolding simulation. This simple coarse-grained model may provide a general and fast approach for the mechanism studies of protein folding.
authors.affiliation: College of Informatics, South China Agricultural University, Guangzhou, China.
authors.forename: Xu-hong
authors.initials: XH
authors.lastname: Tian
authors.forename: Ye-han
authors.initials: YH
authors.lastname: Zheng
authors.forename: Xiong
authors.initials: X
authors.lastname: Jiao
authors.forename: Cai-xing
authors.initials: CX
authors.lastname: Liu
authors.forename: Shan
authors.initials: S
authors.lastname: Chang
mesh_terms: D003198:Computer Simulation; D056004:Molecular Dynamics Simulation; D016011:Normal Distribution; D010455:Peptides / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry; D055550:Protein Stability; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry*; D013049:Spectrin / Q000737:chemistry; D018909:src Homology Domains
chemical_list: D010455:Peptides; D010940:Plant Proteins; D011506:Proteins; C093336:chymotrypsin inhibitor 2; D013049:Spectrin