二芳基乙烯衍生物与DNA结合的分子动力学研究

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.

Molecular Dynamic of Various DNA Sequences Binding of Dithienylethenes†

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.