title: Folding or misfolding: the choice of β-hairpin.
abstract: Proteins fold through complex inter-residue interactions which are mutually supportive and cooperatively lead to thermodynamically favorable native structures. Competing (misfolded) structures, however, could exist, which might affect the thermodynamic and kinetic properties of folded structure. Running long-time REMD simulations on two β-structured polypeptides, the present study identifies the folded and (less populated) competing misfolded states of β-hairpins. Of particular interest is a one-residue shifted misfolded state which has been often seen in previous reports. The folding and misfolding pathways are then energetically characterized by free energy landscape analysis, indicating that the folding and misfolding of β-hairpin are parallel pathways and a protein's selection of following which pathway is a consequence of the competition between the formation of alterable turn configurations and cross-strand hydrophobic interactions. Proteins possessing high percentage of hydrophobic residues introduce strong cross-strand hydrophobic interactions which stabilize the native structural elements in the folding pathway, leading to low possibility of misfolding. The present study provides novel insights into the origin of sequence-dependent β-hairpin misfolding "hidden" behind experimentally detectable β-hairpin folding, suggesting the direction for the structure design of β-structured protein.
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
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; C409585:MRH1 protein, S cerevisiae; D008565:Membrane Proteins; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins