Characterizing the first steps of amyloid formation for the ccbeta peptide.
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.
Strodel
Birgit
B
University Chemical Laboratories, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
Fitzpatrick
Anthony W
AW
Vendruscolo
Michele
M
Dobson
Christopher M
CM
Wales
David J
DJ
D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry; D001704:Biopolymers / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*
D000682:Amyloid; D001704:Biopolymers; D010455:Peptides