Abstract：
The protective innate immune response of β-amyloid peptide (Aβ) has been indicated as a risk factor for Alzheimer\'s disease (AD) due to the rapid amyloidosis. In order to obtain molecular-level insights into the protective and pathogenic roles of Aβ, the binding modes between Aβ1-42 and the envelop glycoprotein D (gD) of Herpes simplex virus-1 (HSV-1)/Aβ1-42 were theoretically investigated by using molecular docking, molecular dynamics (MD) simulations and binding free energy decomposition methods in the present study. The Aβ1-42 stably binds to the envelop gD via intermolecular hydrogen bonds and van der Waals (vdW) interactions. The Aβ1-42 acquires its equilibrium with higher fluctuation amplitude and a better structured C-terminal in the HSV-1 gD-Aβ1-42 complex comparing to that in the Aβ1-42-Aβ1-42 complex. The amino acid residues of Aβ1-42 involved in the formation of the Aβ1-42 dimer are fully free and accessible in the HSV-1 gD-Aβ1-42 complex. It is favorable for the Aβ1-42 monomer to interact with the HSV-1 gD-Aβ1-42 complex. It may be responsible for the rapid amyloidosis which entraps the herpesvirus as well as causing AD.
摘要：
由于快速淀粉样变性,β-淀粉样肽(Aβ)的保护性先天性免疫应答已被认为是阿尔茨海默病(AD)的危险因素。为了获得对Aβ的保护和致病作用的分子水平的见解，利用分子对接理论研究了Aβ1-42与单纯疱疹病毒1(HSV-1)/Aβ1-42包膜糖蛋白D(gD)的结合模式,本研究中的分子动力学(MD)模拟和束缚自由能分解方法。Aβ1-42通过分子间氢键和范德华（vdW）相互作用与包膜gD稳定结合。与Aβ1-42-Aβ1-42复合物相比，Aβ1-42在HSV-1gD-Aβ1-42复合物中以更高的波动幅度和更好的结构C末端获得平衡。参与Aβ1-42二聚体形成的Aβ1-42的氨基酸残基在HSV-1gD-Aβ1-42复合物中是完全游离的和可接近的。Aβ1-42单体与HSV-1gD-Aβ1-42复合物相互作用是有利的。它可能是导致疱疹病毒捕获以及引起AD的快速淀粉样变性的原因。
