title: Molecular dynamics simulation indicating cold denaturation of β-hairpins.
abstract: The folding of a series of β-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 → I(D)PGK) 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 et al. and Dyer et al. Comparative analysis of simulation results for the 5 polypeptides revealed potential mechanism of β-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 β-hairpin structures.
authors: Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. qshao@mail.shcnc.ac.cn
authors: Qiang
authors: Q
authors: Shao
authors: Jiye
authors: J
authors: Shi
authors: Weiliang
authors: W
authors: Zhu
mesh_terms: D000595:Amino Acid Sequence; D003080:Cold Temperature; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011489:Protein Denaturation; D055550:Protein Stability; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D010455:Peptides; D012997:Solvents