Molecular dynamics simulation indicating cold denaturation of ?-hairpins

• Published in: The Journal of chemical physics Vol. 138; no. 8
• Main Authors: Shao, Qiang, Shi, Jiye, Zhu, Weiliang
• Format: Journal Article
• Language: English
• Published: 01.01.2013
• Subjects: Denaturation; Hydrogen bonds; Molecular dynamics; Polypeptides; Series (mathematics); Similarity; Simulation; Stability
• ISSN: 0021-9606
• DOI: 10.1063/1.4792299

The folding of a series of beta -hairpin structured polypeptides, which share high sequence similarity but differ significantly in structure resistance to temperature decrease, was investigated in the present study using integrated-tempering-sampling molecular dynamics simulations on microsecond time scale. MrH3a is a single mutant (I16A) and MrH4a is a double mutant (Y3L/I16A) of the wild-type polypeptide MrH1. MrH3b and MrH4b have an additional mutation in the turn region (INGK arrow right IDPGK) of MrH3a and MrH4a, respectively. It was observed in the present study that the cold denaturation tendency follows the order of MrH1 > MrH4a > MrH3a, while the folded structures of MrH3b and MrH4b have the enhanced stability and are not subject to cold denaturation. These observations are in good agreement with experimental results of Maynard and Dyer Comparative analysis of simulation results for the 5 polypeptides revealed potential mechanism of beta -hairpin cold denaturation. The main determinant of cold denaturation tendency is likely the stability decrease of backbone hydrogen bonds at low temperatures, which in turn is affected by the packing manner of the hydrophobic core cluster of beta -hairpin structures.