The Free Energy Landscape for β Hairpin Folding in Explicit Water

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 26; pp. 14931 - 14936
• Main Authors: Zhou, Ruhong, Berne, Bruce J., Germain, Robert
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.12.2001; National Acad Sciences; The National Academy of Sciences
• Subjects: Amino Acid Sequence; Biological Sciences; Coordinate systems; Energy; Force field; Free energy; Gyration; High temperature; Hydrogen bonds; Local minimum; Low temperature; Molecular biology; Molecular Sequence Data; Nerve Tissue Proteins - chemistry; Nuclear Magnetic Resonance, Biomolecular; Protein Folding; Proteins; Solvents; Temperature; Water; Water - chemistry
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.201543998

The folding free energy landscape of the C-terminal β hairpin of protein G has been explored in this study with explicit solvent under periodic boundary condition and Oplsaa force field. A highly parallel replica exchange method that combines molecular dynamics trajectories with a temperature exchange Monte Carlo process is used for sampling with the help of a new efficient algorithm P3ME/RESPA. The simulation results show that the hydrophobic core and the β strand hydrogen bond form at roughly the same time. The free energy landscape with respect to various reaction coordinates is found to be rugged at low temperatures and becomes a smooth funnel-like landscape at about 360 K. In contrast to some very recent studies, no significant helical content has been found in our simulation at all temperatures studied. The β hairpin population and hydrogen-bond probability are in reasonable agreement with the experiment at biological temperature, but both decay more slowly than the experiment with temperature.