title: Robustness in protein folding revealed by thermodynamics calculations.
abstract: Long-range intraprotein interactions play important roles in protein folding. In the present study, we use two variants of the B domain of protein A (BdpA F14W/G30A and BdpA_ds) and two variants of the Trp cage (TC5b_P1 and TC5b_P2) as models to investigate how long-range hydrophobic interactions affect protein tertiary and secondary structures. The mutation of the selected residues (BdpA F14W/G30A) or the change in the sequence order of Helix1 and Helix2 (BdpA_ds) changes detailed hydrophobic interactions. However, this change does not alter the global three-helix-bundle structure of BdpA and the overall shape of the folding free-energy landscape. It does affect the formation and stability of individual secondary structures. Similarly, the addition of an extra segment to the C-terminus of Trp-cage increases the number of long-range hydrophobic interactions without making any significant change of the native structure of Trp-cage. These results show the robustness of the overall protein folding, where rather large sequence changes exert significant influences on secondary but not tertiary structures.
authors.affiliation: Institute of Theoretical and Computational Chemistry, College of Chemistry and Molecular Engineering, Beijing National Laboratory of Molecular Sciences, Peking University, Beijing 100871, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shao
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
authors.forename: Yi Qin
authors.initials: YQ
authors.lastname: Gao
mesh_terms: D056004:Molecular Dynamics Simulation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012997:Solvents / Q000737:chemistry; D013205:Staphylococcal Protein A / Q000737:chemistry*; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
chemical_list: D012997:Solvents; D013205:Staphylococcal Protein A; D014364:Tryptophan