高等学校化学学报 ›› 2019, Vol. 40 ›› Issue (6): 1229-1235.doi: 10.7503/cjcu20180837

• 物理化学 • 上一篇    下一篇

二芳基乙烯衍生物与DNA结合的分子动力学研究

孙浩帆1,2, 张凌怡1, PATRICKNorman2, 张维冰1()   

  1. 1. 华东理工大学, 上海市功能材料化学重点实验室, 上海 210036
    2. 瑞典皇家理工学院, 斯德哥尔摩 SE-106 91
  • 收稿日期:2018-12-13 出版日期:2019-06-10 发布日期:2019-04-04
  • 作者简介:

    联系人简介: 张维冰, 男, 博士, 教授, 博士生导师, 主要从事色谱固定相、 多维色谱理论与应用研究. E-mail: weibingzhang@ecust.edu.cn

  • 基金资助:
    国家自然科学基金(批准号: 21475044)、 国家科技支撑项目(批准号: 2015BAK44B00)、 中央高校基本科研专项资金(批准号: 222201817022)和国家留学基金(批准号: 201706745036)资助.

Molecular Dynamic of Various DNA Sequences Binding of Dithienylethenes

SUN Haofan1,2, ZHANG Lingyi1, PATRICK Norman2, ZHANG Weibing1()   

  1. 1. Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, China
    2. KTH Royal Institute of Technology, Stockholm SE-106 91, Sweden
  • Received:2018-12-13 Online:2019-06-10 Published:2019-04-04
  • Supported by:
    † Supported by the National Natural Science Foundation of China(No.21475044), the National Key Technology R&D Program, China(No.2015BAK44B00), the Fundamental Research Funds for the Central Universities, China(No.222201817022) and the Chinese Scholarship Council, China(No.201706745036).

摘要:

基于分子动力学方法, 对2种旋转异构的二芳基乙烯(DTE, dithienylethene)衍生物(DTE1和DTE2)与不同分子结构DNA结合过程的热力学与动力学特征进行模拟, 结果发现, DTE1, DTE2与DNA分子采用小凹槽结合(MiGB)的模式结合时所需能量最低, 存在的分子间库仑能与范德华相互作用能最小, 说明该结合模式最稳定; 由于空间位阻作用, 互为旋转异构体的2个DTE衍生物与DNA作用表现出截然不同的结合行为, DNA对DTE衍生物具有明显的对映异构体选择性; DTE衍生物与DNA分子作用位点的选择性直接与构成位点的碱基对相关.

关键词: 分子动力学模拟, 手性药物, 二芳基乙烯衍生物, DNA, 旋转异构体, 结合模式

Abstract:

Binding modes between various DNA sequences and stereoisomeric rotamers of two dithienylethene derivatives(DTE1 and DTE2) representing photochromic switches were investigated in terms of molecular dynamics simulations and characterized by their binding energies. The result shows that minor groove binding(MiGB) is found to be the most robust binding mode between DNA and DTE(either DTE1 or DTE2). Due to steric hindrance, two DTE derivatives that are rotatable isomers exhibit distinct binding behaviors to DNA, and thus DNA has significant enantioselectivity for DTE derivatives. Moreover, the selectivity of the DTE derivative to the binding site of the DNA molecule is directly related to the base pair constitution, providing accurate theoretical guidance for precision medicine by chiral drugs based on this molecule.

Key words: Molecular dynamics, Chiral drug, Dithienylethene, DNA, Rotamer, Binding mode

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