Exploring the Mechanism of Inhibition of Au Nanoparticles on the Aggregation of Amyloid-?(16-22) Peptides at the Atom Level by All-Atom Molecular Dynamics.

ABSTRACT: The abnormal self-assembly of the amyloid-? peptide into toxic ?-rich aggregates can cause Alzheimer’s disease. Recently, it has been shown that small gold nanoparticles (AuNPs) inhibit A? aggregation and fibrillation by slowing down the nucleation process in experimental studies. However, the effects of AuNPs on A? oligomeric structures are still unclear. In this study, we investigate the conformation of A?(16-22) tetramers/octamers in the absence and presence of AuNPs using extensive all-atom molecular-dynamics simulations in explicit solvent. Our studies demonstrate that the addition of AuNPs into A?(16-22) solution prevents ?-sheet formation, and the inhibition depends on the concentration of A?(16-22) peptides. A detailed analysis of the A?(16-22)/A?(16-22)/water/AuNPs interactions reveals that AuNPs inhibit the ?-sheet formation resulting from the same physical forces: hydrophobic interactions. Overall, our computational study provides evidence that AuNPs are likely to inhibit A?(16-22) and full-length A? fibrillation. Thus, this work provides theoretical insights into the development of inorganic nanoparticles as drug candidates for treatment of AD.

SUBMITTER: Song M 

PROVIDER: S-EPMC6032210 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature