Computational assessment of the impact of Cu(II) and Al(III) on β-amyloid₄₂ fibrils: Binding sites, structural stability, and possible physiological implications.

ABSTRACT: One of Alzheimer's disease major hallmarks is the aggregation of β-amyloid peptide, a process in which metal ions play an important role. In the present work, an integrative computational study has been performed to identify the metal-binding regions and determine the conformational impact of Cu(II) and Al(III) ion binding to the β-amyloid (Aβ₄₂) fibrillary structure. Through classical and Gaussian accelerated molecular dynamics, it has been observed that the metal-free fiber shows a hinge fan-like motion of the S-shaped structure, maintaining the general conformation. Upon metal coordination, distinctive patterns are observed depending on the metal. Cu(II) binds to the flexible N-terminal region and induces structural changes that could ultimately disrupt the fibrillary structu

SUBMITTER: Roldan-Martin L 

PROVIDER: S-EPMC9940836 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature