Diversity of kinetic pathways in amyloid fibril formation.
The kinetics of peptide oligomerization was investigated using Langevin Dynamics simulations and a coarse-grained peptide model. The simulations show a rich diversity of aggregation pathways, modulated by the beta-sheet propensity (flexibility) of the peptide. Aggregation into amyloidlike fibrils occurs via three main mechanisms: (i) formation of fibrils directly from the assembly of early ordered oligomers, (ii) fibril formation via the formation of on-pathway, nonfibrillar aggregates high in beta-sheet content, and (iii) formation of amorphous aggregates followed by reorganization to beta-sheet aggregates and to fibrils. beta-sheet, nonfibrillar aggregates also appeared as long-lived, "off-pathway" end-product species.
Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, California 93106, USA. gbellesia@chem.ucsb.edu
Giovanni
G
Bellesia
Joan-Emma
JE
Shea
D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003198:Computer Simulation; D007700:Kinetics; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D020836:Protein Structure, Quaternary
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010455:Peptides