Center S3, CNR Institute of Nanoscience, via Campi 213/A, 41125 Modena, Italy.
SISSA-Scuola Internazionale Superiore di Studi Avanzati, via Bonomea 265, 34136 Trieste, Italy.
Nanoscale. 2017 Feb 9;9(6):2279-2290. doi: 10.1039/c6nr06010b.
Proteins in the proximity of inorganic surfaces and nanoparticles may undergo profound adjustments that trigger biomedically relevant processes, such as protein fibrillation. The mechanisms that govern protein-surface interactions at the molecular level are still poorly understood. In this work, we investigate the adsorption onto a gold surface, in water, of an amyloid-β (Aβ) peptide, which is the amyloidogenic peptide involved in Alzheimer's disease. The entire adsorption process, from the peptide in bulk water to its conformational relaxation on the surface, is explored by large-scale atomistic molecular dynamics (MD) simulations. We start by providing a description of the conformational ensemble of Aβ in solution by a 22 μs temperature replica exchange MD simulation, which is consistent with previous results. Then, we obtain a statistical description of how the peptide approaches the gold surface by multiple MD simulations, identifying the preferential gold-binding sites and giving a kinetic picture of the association process. Finally, relaxation of the Aβ conformations at the gold/water interface is performed by a 19 μs Hamiltonian-temperature replica exchange MD simulation. We find that the conformational ensemble of Aβ is strongly perturbed by the presence of the surface. In particular, at the gold/water interface the population of the conformers akin to amyloid fibrils is significantly enriched, suggesting that this extended contact geometry may promote fibrillation.
在无机表面和纳米颗粒附近的蛋白质可能会发生深刻的调整，从而引发与生物医学相关的过程，如蛋白质纤维化。在分子水平上控制蛋白质-表面相互作用的机制仍知之甚少。在这项工作中，我们研究了一种淀粉样β（Aβ）肽在水中吸附到金表面的情况，该肽是与阿尔茨海默病相关的淀粉样肽。通过大规模原子分子动力学（MD）模拟，研究了从肽在本体水中到其在表面上的构象弛豫的整个吸附过程。我们首先通过 22 μs 温度交换 MD 模拟对 Aβ在溶液中的构象系综进行描述，该模拟结果与以前的结果一致。然后，通过多次 MD 模拟获得了肽接近金表面的统计描述，确定了优先结合金的位点，并给出了结合过程的动力学图像。最后，通过 19 μs 的哈密顿温度交换 MD 模拟对 Aβ在金/水界面的构象弛豫进行了研究。我们发现，表面的存在强烈地干扰了 Aβ的构象系综。特别是在金/水界面处，类似于淀粉样纤维的构象的丰度显著增加，这表明这种扩展的接触几何形状可能促进纤维化。
