位置:成果数据库 > 期刊 > 期刊详情页
富勒烯与β淀粉样肽低聚体结合的分子动力学模拟
  • ISSN号:1000-6818
  • 期刊名称:《物理化学学报》
  • 时间:0
  • 分类:O641[理学—物理化学;理学—化学]
  • 作者机构:[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
  • 相关基金:国家自然科学基金(11274075)资助项目.周晓颖感谢秦惠若与李政道中国大学生见习进修基金(CURE)对其研究的资助.
中文摘要:

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Turn27-31位点(27NKGAl31)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Turn27-31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.

英文摘要:

We investigated the binding process of fullerene to fibrillike 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) (27LVFFA21) and the turn region (27NKGAl31) 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. Structural disruption was observed under two conditions; in cases where the fullerene exhibited a tendency to insert into the CHC region of the Aβ β-sheet bilayer and in situations where the fullerene molecule broke the main-chain hydrogen bond in the N-terminal region of the peptides. These two processes assist in understanding the mechanism whereby fullerene inhibits Aβ42 aggregation. Additionally, the grooverolling mechanism at the turn associated with the 27-31 and Y10-H14 sites was identified. Owing to the periodic features of amyloid fibrils, the fullerene could roll along the elongation direction of the Aβ protofibril on certain grooves. This mechanism could be helpful in predicting the interactions of fullerene with other amyloid peptides or proteins.

同期刊论文项目
同项目期刊论文
期刊信息
  • 《物理化学学报》
  • 中国科技核心期刊
  • 主管单位:中国科学技术协会
  • 主办单位:北京大学化学与分子工程学院承办
  • 主编:刘忠范
  • 地址:北京大学化学楼
  • 邮编:100871
  • 邮箱:whxb@pku.edu.cn
  • 电话:010-62751724
  • 国际标准刊号:ISSN:1000-6818
  • 国内统一刊号:ISSN:11-1892/O6
  • 邮发代号:82-163
  • 获奖情况:
  • 中文核心期刊
  • 国内外数据库收录:
  • 俄罗斯文摘杂志,美国化学文摘(网络版),荷兰文摘与引文数据库,美国科学引文索引(扩展库),英国科学文摘数据库,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),英国英国皇家化学学会文摘,中国北大核心期刊(2000版)
  • 被引量:24781