College of Mathematics and Physics, Shanghai University of Electric Power, Shanghai 200090, China.
College of Energy and Mechanical Engineering, Shanghai University of Electric Power, Shanghai 200090, China.
Int J Mol Sci. 2018 Jun 20;19(6):1815. doi: 10.3390/ijms19061815.
The abnormal self-assembly of the amyloid-β peptide into toxic β-rich aggregates can cause Alzheimer’s disease. Recently, it has been shown that small gold nanoparticles (AuNPs) inhibit Aβ aggregation and fibrillation by slowing down the nucleation process in experimental studies. However, the effects of AuNPs on Aβ oligomeric structures are still unclear. In this study, we investigate the conformation of Aβ(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 Aβ(16-22) solution prevents β-sheet formation, and the inhibition depends on the concentration of Aβ(16-22) peptides. A detailed analysis of the Aβ(16-22)/Aβ(16-22)/water/AuNPs interactions reveals that AuNPs inhibit the β-sheet formation resulting from the same physical forces: hydrophobic interactions. Overall, our computational study provides evidence that AuNPs are likely to inhibit Aβ(16-22) and full-length Aβ fibrillation. Thus, this work provides theoretical insights into the development of inorganic nanoparticles as drug candidates for treatment of AD.
淀粉样蛋白-β肽的异常自组装成有毒的富含β的聚集体可导致阿尔茨海默病。最近的研究表明，小金纳米粒子（AuNPs）通过减缓实验研究中的成核过程来抑制 Aβ 聚集和纤维化。然而，AuNPs 对 Aβ 低聚物结构的影响尚不清楚。在这项研究中，我们使用明确定义溶剂中的全原子分子动力学模拟来研究 AuNPs 存在与否时 Aβ（16-22）四聚体/八聚体的构象。我们的研究表明，AuNPs 的加入可防止 Aβ（16-22）溶液中β-折叠的形成，而抑制作用取决于 Aβ（16-22）肽的浓度。对 Aβ（16-22）/Aβ（16-22）/水/AuNPs 相互作用的详细分析表明，AuNPs 抑制β-折叠的形成是由于相同的物理力：疏水相互作用。总体而言，我们的计算研究为 AuNPs 可能抑制 Aβ（16-22）和全长 Aβ 纤维化提供了证据。因此，这项工作为将无机纳米粒子作为治疗 AD 的药物候选物的开发提供了理论见解。
