Discrete molecular dynamics study of oligomer formation by N-terminally truncated amyloid β-protein.

ABSTRACT: In Alzheimer's disease (AD), amyloid β-protein (Aβ) self-assembles into toxic oligomers. Of the two predominant Aβ alloforms, Aβ1-40 and Aβ1-42, the latter is particularly strongly linked to AD. N-terminally truncated and pyroglutamated Aβ peptides were recently shown to seed Aβ aggregation and contribute significantly to Aβ-mediated toxicity, yet their folding and assembly were not explored computationally. Discrete molecular dynamics approach previously captured in vitro-derived distinct Aβ1-40 and Aβ1-42 oligomer size distributions and predicted that the more toxic Aβ1-42 oligomers had more flexible and solvent-exposed N-termini than Aβ1-40 oligomers. Here, we examined oligomer formation of Aβ3-40, Aβ3-42, Aβ11-40, and Aβ11-42 by the discrete molecular dynamics approach. The four N-term

SUBMITTER: Meral D 

PROVIDER: S-EPMC3665754 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature