Itoh Satoru G, Okumura Hisashi
Department of Theoretical and Computational Molecular Science, Institute for Molecular Science , Okazaki, Aichi 444-8585, Japan.
Department of Structural Molecular Science, The Graduate University for Advanced Studies , Okazaki, Aichi 444-8585, Japan.
J Phys Chem B. 2016 Jul 14;120(27):6555-61. doi: 10.1021/acs.jpcb.6b03828. Epub 2016 Jun 24.
Oligomers of amyloid-β peptides (Aβ) are formed during the early stage of the amyloidogenesis process and exhibit neurotoxicity. The oligomer formation process of Aβ and even that of Aβ fragments are still poorly understood, though understanding of these processes is essential for remedying Alzheimer's disease. In order to better understand the oligomerization process of the C-terminal Aβ fragment Aβ(29-42) at the atomic level, we performed the Hamiltonian replica-permutation molecular dynamics simulation with Aβ(29-42) molecules using the explicit water solvent model. We observed that oligomers increased in size through the sequential addition of monomers to the oligomer, rather than through the assembly of small oligomers. Moreover, solvent effects played an important role in this oligomerization process.
淀粉样β肽（Aβ）寡聚体在淀粉样蛋白生成过程的早期形成，并具有神经毒性。尽管了解这些过程对于治疗阿尔茨海默病至关重要，但Aβ的寡聚体形成过程乃至Aβ片段的寡聚体形成过程仍知之甚少。为了在原子水平上更好地理解C端Aβ片段Aβ(29 - 42)的寡聚化过程，我们使用显式水溶剂模型对Aβ(29 - 42)分子进行了哈密顿副本置换分子动力学模拟。我们观察到，寡聚体通过单体依次添加到寡聚体中而增大尺寸，而不是通过小寡聚体的组装。此外，溶剂效应在这个寡聚化过程中起着重要作用。
