The role of sidechain packing and native contact interactions in folding: Discontinuous molecular dynamics folding simulations of an all-atom Go model of fragment B of Staphylococcal protein A

摘要

Protein topology, which refers to the arrangement of secondary structures of proteins, has been extensively investigated to examine its role in protein folding. However, recent studies show that topology alone cannot account for the variation of folding behaviors observed in some proteins of the same structural family In a recent work, we showed that the native structure of the second beta hairin of protein G predicts a folding mechanism that is different from topology-based models. Here, we continue to examine bow much one can learn about folding mechanism from natve structure. This workj focuses to examine how much one can learn about folding mechanpolar hydrogen)Go model interacting with simple discontinuous potentials, the folding of the model BpA was observed in 112 out of 249 trajectories within 50 h of CPU times on a Pentium PC (1 GHz). The model successfully captured several specific properties of BpA that have been observed experimentally. H_2-H_3 microdomain compared to the H_1-H_2 microdomain. These specific details were not produced by a topology-based square-well model of BpA. Thus, the result further supports the important role of sidechain packing in determining the specific pathway of protein folding. Additional 96 000 short simulations were performed to locate the transition states of the two folding pathways. The limitation of the Go model and its possible improvement are also discussed.