Dynamics of locking of peptides onto growing amyloid fibrils.

ABSTRACT: Sequence-dependent variations in the growth mechanism and stability of amyloid fibrils, which are implicated in a number of neurodegenerative diseases, are poorly understood. We have carried out extensive all-atom molecular dynamics simulations to monitor the structural changes that occur upon addition of random coil (RC) monomer fragments from the yeast prion Sup35 and Abeta-peptide onto a preformed fibril. Using the atomic resolution structures of the microcrystals as the starting points, we show that the RC --> beta-strand transition for the Sup35 fragment occurs abruptly over a very narrow time interval, whereas the acquisition of strand content is less dramatic for the hydrophobic-rich Abeta-peptide. Expulsion of water, resulting in the formation of a dry interface between 2 adjacent

SUBMITTER: Reddy G 

PROVIDER: S-EPMC2715474 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature