物理化学学报 >> 2014, Vol. 30 >> Issue (8): 1587-1596.doi: 10.3866/PKU.WHXB201405291

生物物理化学 上一篇    

富勒烯与β淀粉样肽低聚体结合的分子动力学模拟

周晓颖, 郗文辉, 韦广红   

  1. 应用表面物理国家重点实验室, 计算物质科学教育部重点实验室, 复旦大学物理系, 上海 200433
  • 收稿日期:2014-04-11 修回日期:2014-05-28 发布日期:2014-07-18
  • 通讯作者: 韦广红 E-mail:ghwei@fudan.edu.cn
  • 基金资助:

    国家自然科学基金(11274075)资助项目.

Molecular Dynamics Simulations on the Binding of Fullerene to Amyloid-β Oligomers

ZHOU Xiao-Ying, XI Wen-Hui, WEI Guang-Hong   

  1. Department of Physics, Fudan University, Key Laboratory for Computational Physical Sciences Ministry of Education, State Key Laboratory of Surface Physics, Shanghai 200433, P. R. China
  • Received:2014-04-11 Revised:2014-05-28 Published:2014-07-18
  • Contact: WEI Guang-Hong E-mail:ghwei@fudan.edu.cn
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (11274075).

摘要:

本文通过分子动力学模拟研究富勒烯在Aβ42 低聚体表面的结合过程. 在结合过程中,C60在Aβ表面经历一系列尝试过程,最终找到某个稳定的结合位点. 根据结合的残基不同,这些结合位点可以分为六类,其中核心疏水区域(CHC)位点(17LVFFA21)及Turn 27-31 位点(27NKGAI31)具有最强的结合稳定性. 二者的结合主要通过范德华作用稳定,而溶剂化效应则起相反作用. 在这六类位点中的两个位点,观察到C60会对Aβ二级结构起破坏作用. 其一位于核心疏水区域,C60有挤入多肽β片层中间的趋势;另外一位点位于N端,C60能够破坏外侧Aβ的3-5 号残基的主链氢键,瓦解其末端的β片结构. 这两个过程对理解富勒烯抑制Aβ聚集的微观机制提供了帮助. 此外,在Turn 27-31 位点以及Y10-H14 位点,发现了富勒烯与Aβ纤维样聚集体结合的沟槽滚动机制,即富勒烯能够在淀粉样低聚体表面形成的特定沟槽内滚动. 这一特征有助于预测富勒烯在其它淀粉样多肽表面的结合位点及结合行为.

关键词: 多位点结合, 结合能, 二级结构破坏, 疏水口袋, 沟槽滚动机制

Abstract:

We investigated the binding process of fullerene to fibril-like Aβ42 oligomers by performing multiple molecular dynamics simulations. It was observed that the C60 molecule searched a series of positions on the surfaces of the Aβ42 oligomers before finding a stable binding state. Multi-binding sites have been identified and these can be classified into six types according to the type of residue in contact with the fullerene. The sites near the central hydrophobic core (CHC) (17LVFFA21) and the turn region (27NKGAI31) were identified as the most suitable sites with the lowest associated binding energies. These bound states were primarily stabilized by van der Waals interactions, while the solvation effect acted as a destabilizing factor.

Key words: Multi-site binding, Binding energy, Secondary structure disruption, Hydrophobic cave, Groove-rolling mechanism

MSC2000: 

  • O641