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Updated: May 17, 2026

Thermodynamics of Membrane Protein Folding Measured by Fluorescence Spectroscopy
Published on: April 28, 2011
Robustness in protein folding revealed by thermodynamics calculations
Qiang Shao1, Weiliang Zhu, Yi Qin Gao
1Institute of Theoretical and Computational Chemistry, College of Chemistry and Molecular Engineering, Beijing National Laboratory of Molecular Sciences, Peking University, Beijing 100871, China.
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.
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