title: Conformational characteristics of unstructured peptides: alpha-synuclein.
abstract: We have performed replica-exchange molecular dynamics simulations on 41 residue peptides containing NAC region of alpha-synuclein in various force fields and solvent conditions. Alpha-synuclein is known to be the major cause of Parkinson's disease by amyloid-like aggregation, and one of the natively unfolded proteins. To investigate conformational characteristics of intrinsically unstructured peptides, we carried out structural analysis by introducing 'representative structure' for ensemble of structures occurring during the overall trajectory. Representative structures may be defined by using either coordinate averaging or distance averaging. When applied to the natively folded proteins such as villin headpiece, structural analysis based on representative structure was found to yield consistent results with those obtained from conventional analysis. Individual conformations obtained from the simulations of NAC peptide for various conditions show flexible structures close to random coil. Secondary structure contents and free energy surfaces showed dependency on solvent conditions, which may be interpreted as another manifestation of structural diversity. It is found that representative structures can provide useful information about structural characteristics of intrinsically unstructured proteins.
authors.affiliation: School of Chemistry, Seoul National University, Seoul 151-747, Korea.
authors.forename: Jeseong
authors.initials: J
authors.lastname: Yoon
authors.forename: Joonho
authors.initials: J
authors.lastname: Park
authors.forename: Soonmin
authors.initials: S
authors.lastname: Jang
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Lee
authors.forename: Seokmin
authors.initials: S
authors.lastname: Shin
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012997:Solvents / Q000737:chemistry; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D016900:Neurofilament Proteins; D010446:Peptide Fragments; D010455:Peptides; D012997:Solvents; D051844:alpha-Synuclein; C115223:villin headpiece subdomain peptide