Aggregating the amyloid Abeta(11-25) peptide into a four-stranded beta-sheet structure.
We present a detailed analysis of the structural properties of one monomer of Abeta(11-25) as well as of the aggregation mechanisms for four chains of Abeta(11-25) using the activation-relaxation technique coupled with a generic energy potential. Starting from a random distribution of these four chains, we find that the system assembles rapidly into a random globular state that evolves into three- and four-stranded antiparallel beta-sheets. The aggregation process is considerably accelerated by the presence of preformed dimers. We also find that the reptation mechanism already identified in shorter peptides plays a significant role here in allowing the structure to reorganize without having to fully dissociate.
Boucher
Geneviève
G
Département de Physique and Centre Robert-Cedergren en bioinformatique, Université de Montréal, C.P. 6128, Succursale Centre-ville Montréal, Québec H3C 3J7, Canada.
Mousseau
Normand
N
Derreumaux
Philippe
P
D000595:Amino Acid Sequence; D003198:Computer Simulation; D019281:Dimerization; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D000685:Serum Amyloid A Protein / Q000737:chemistry* / Q000378:metabolism
D000685:Serum Amyloid A Protein