Mechanistic Kinetic Model Reveals How Amyloidogenic Hydrophobic Patches Facilitate the Amyloid-β Fibril Elongation.

ABSTRACT: Abnormal aggregation of amyloid β (Aβ) peptides into fibrils plays a critical role in the development of Alzheimer's disease. A two-stage "dock-lock" model has been proposed for the Aβ fibril elongation process. However, the mechanisms of the Aβ monomer-fibril binding process have not been elucidated with the necessary molecular-level precision, so it remains unclear how the lock phase dynamics leads to the overall in-register binding of the Aβ monomer onto the fibril. To gain mechanistic insights into this critical step during the fibril elongation process, we used molecular dynamics (MD) simulations with a physics-based coarse-grained UNited-RESidue (UNRES) force field and sampled extensively the dynamics of the lock phase process, in which a fibril-bound Aβ_(9-40) peptide rear

SUBMITTER: Xie H 

PROVIDER: S-EPMC8986627 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature