Impact of Mutations on the Conformational Transition from α-Helix to β-Sheet Structures in Arctic-Type Aβ₄₀: Insights from Molecular Dynamics Simulations.

ABSTRACT: The amyloid-β (Aβ) protein aggregation into toxic oligomers and fibrils has been recognized as a key player in the pathogenesis of Alzheimer's disease. Recent experiments reported that a double alanine mutation (L17A/F19A) in the central hydrophobic core (CHC) region of [G22]Aβ₄₀ (familial Arctic mutation) diminished the self-assembly propensity of [G22]Aβ₄₀. However, the molecular mechanism behind the decreased aggregation tendency of [A17/A19/G22]Aβ₄₀ is not well understood. Herein, we carried out molecular dynamics simulations to elucidate the structure and dynamics of [G22]Aβ₄₀ and [A17/A19/G22]Aβ₄₀. The results for the secondary structure analysis reveal a significantly increased amount of the helical content in the CHC and C-term

SUBMITTER: Saini RK 

PROVIDER: S-EPMC7495726 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature