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

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.