We have performed replica-exchange molecular dynamics simulations on 41 residue peptides containing NAC region of α-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.

Key words: Replica-exchange; α-synuclein; Natively unstructured protein; Villin headpiece; and Representative structure.