Structural diversity of Alzheimer's disease amyloid-β dimers and their role in oligomerization and fibril formation.

ABSTRACT: Alzheimer's disease (AD) is associated with the formation of toxic amyloid-β (Aβ)42 oligomers, and recent evidence supports a role for Aβ dimers as building blocks for oligomers. Molecular dynamics simulation studies have identified clans for the dominant conformations of Aβ42 forming dimers; however, it is unclear if a larger spectrum of dimers is involved and which set(s) of dimers might evolve to oligomers verse fibrils. Therefore, for this study we generated multiple structural conformations of Aβ42, using explicit all-atom molecular dynamics, and then clustering the different structures based on key conformational similarities. Those matching a selection threshold were then used to model a process of oligomerization. Remarkably, we showed a greater diversity in Aβ dimers than previous

SUBMITTER: Tsigelny IF 

PROVIDER: S-EPMC4449729 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature