title: The universality of β-hairpin misfolding indicated by molecular dynamics simulations.
abstract: Previous molecular dynamics simulations showed that besides the experimentally measured folded structures, several β-structured polypeptides could also have misfolded "out-of-register" structures. Through the enhanced sampling molecular dynamics simulations on a series of polypeptides using either implicit or explicit solvent model, the present study systematically investigated the universality of β-hairpin misfolding and its determinants. It was observed that the misfolding could take place for almost all polypeptides under study, especially in the presence of weak side chain hydrophobicity. Moreover, the observed misfolded structures for various polypeptides share the following common features: (1) the turn length in misfolded structure is one-residue shorter than that in folded structure; (2) the hydrophobic side chains on the two strands are pointed to the opposite directions instead of packing in the same direction to form hydrophobic core cluster in the folded structure; and (3) the misfolded structure is one-residue-shifted asymmetric β-hairpin structure. The detailed analysis suggested that the misfolding of β-hairpin is the result of the competition between the formation of the alterable turn configurations and the inter-strand hydrophobic interactions. These predictions are desired to be tested by experiments.
authors.affiliation: Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shao
authors.forename: Jinan
authors.initials: J
authors.lastname: Wang
authors.forename: Jiye
authors.initials: J
authors.lastname: Shi
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000595:Amino Acid Sequence; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry
chemical_list: D010455:Peptides; D012997:Solvents