Multiple long molecular dynamics simulations are used to probe the oligomerization mechanism of Aβ16-22 (KLVFFAE) peptides. The peptides, in the monomeric form, adopt either compact random-coil or extended β strand-like structures. The assembly of the low-energy oligomers, in which the peptides form antiparallel β sheets, occurs by multiple pathways with the formation of an obligatory α-helical intermediate. This observation and the experimental results on fibrillogenesis of Aβ1-40 and Aβ1-42 peptides suggest that the assembly mechanism (random coil → α helix → β strand) is universal for this class of peptides. In Aβ16-22 oligomers both interpeptide hydrophobic and electrostatic interactions are critical in the formation of the antiparallel β sheet structure. Mutations of either hydrophobic or charged residues destabilize the oligomer, which implies that the 16-22 fragments of Arctic (E22G), Dutch (E22Q), and Italian (E22K) mutants are unlikely to form ordered fibrils.
Klimov, D. K., & Thirumalai, D. (2003). Dissecting the assembly of Aβ16-22 amyloid peptides into antiparallel β sheets. Structure, 11(3), 295–307. https://doi.org/10.1016/S0969-2126(03)00031-5