title: Characterizing the first steps of amyloid formation for the ccbeta peptide.
abstract: We employ constant-temperature and replica exchange molecular dynamics to survey the free energy landscape of the ccbeta peptide using a united-atom potential and an implicit solvent representation. Starting from the experimental coiled-coil structure we observe alpha to beta conversion on increasing the temperature, in agreement with experiment. Various beta-sheet trimers are identified as free energy minima, including one that closely resembles the amyloid beta-sheet model previously proposed from experimental data. We characterize two alternative pathways leading to beta-sheets. The first proceeds via direct alpha to beta conversion without dissociation of the trimer, and the second can be classified as a dissociation/reassociation pathway.
authors.affiliation: University Chemical Laboratories, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Birgit
authors.initials: B
authors.lastname: Strodel
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Fitzpatrick
authors.forename: Michele
authors.initials: M
authors.lastname: Vendruscolo
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.forename: David J
authors.initials: DJ
authors.lastname: Wales
mesh_terms: D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry; D001704:Biopolymers / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*
chemical_list: D000682:Amyloid; D001704:Biopolymers; D010455:Peptides