School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
J Phys Chem B. 2012 Jun 28;116(25):7428-35. doi: 10.1021/jp3034209. Epub 2012 Jun 18.
Aβ oligomers are potential targets for the diagnosis and therapy of Alzheimer's disease (AD). On the other hand, the molecule curcumin has been shown to possess significant therapeutic potential in many areas. In this paper, we use all-atom explicit solvent molecular dynamics simulations to study the effect of curcumin on the stability of Aβ amyloid protein oligomers. We observed that curcumin decreases the β-sheet secondary structural content within the Aβ oligomers without reducing the contacts between the monomers. The breaking of the β-sheet is found to be preceded by a deformation of the β-sheet structure due to hydrophobic interaction from the nearby curcumin. Furthermore, the π-stacking interaction between curcumin (keto ring and enol ring) and the aromatic residues of Aβ, which exists throughout the simulations, has also contributed to the diminishing of the β-sheet structure. Our analysis of the underwrapped amide-carbonyl hydrogen bonds reveals several stable dehydrons of the oligomer, especially the dehydron pair 34L and 41I, which curcumin tends to hover over. We have examined the paths of curcumin on the Aβ proteins and determined the common routes where curcumin lingers as it traverses around the Aβ. In consequence, our study has provided a detailed interaction picture between curcumin and the Aβ oligomers.
β-淀粉样蛋白寡聚体是阿尔茨海默病（AD）诊断和治疗的潜在靶点。另一方面，姜黄素已被证明在许多领域具有显著的治疗潜力。在本文中，我们使用全原子显式溶剂分子动力学模拟研究姜黄素对 Aβ 淀粉样蛋白寡聚体稳定性的影响。我们观察到姜黄素降低了 Aβ 寡聚体中的β-折叠二级结构含量，而不会减少单体之间的接触。发现在β-折叠结构断裂之前，由于附近姜黄素的疏水相互作用，β-折叠结构发生了变形。此外，姜黄素（酮环和烯醇环）与 Aβ 中芳香族残基之间的π-堆积相互作用在整个模拟过程中都存在，这也导致了β-折叠结构的减少。我们对未包裹酰胺羰基氢键的分析揭示了寡聚体的几个稳定脱水物，特别是脱水物对 34L 和 41I，姜黄素倾向于盘旋在这些脱水物上。我们已经检查了姜黄素在 Aβ 蛋白上的路径，并确定了姜黄素在围绕 Aβ 运动时停留的常见路径。因此，我们的研究提供了姜黄素与 Aβ 寡聚体之间详细的相互作用图。
