物理化学学报 >> 2008, Vol. 24 >> Issue (10): 1917-1921.doi: 10.3866/PKU.WHXB20081031

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DNA小沟结合二脒:水分子的识别作用

马国正; 求亚芳; 南俊民; 肖信   

  1. 华南师范大学化学与环境学院, 广州 510006
  • 收稿日期:2008-06-09 修回日期:2008-07-10 发布日期:2008-10-08
  • 通讯作者: 马国正 E-mail:gzma@scnu.edu.cn

DNA Minor Groove Binding by Diamidine:Water Molecule in Ligand Recognition

MA Guo-Zheng; QIU Ya-Fang; NAN Jun-Min; XIAO Xin   

  1. School of Chemistry &Environment, South China Normal University, Guangzhou 510006, P. R. China
  • Received:2008-06-09 Revised:2008-07-10 Published:2008-10-08
  • Contact: MA Guo-Zheng E-mail:gzma@scnu.edu.cn

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摘要： 采用分子动力学模拟了DB921-DNA复合物, 通过7 ns的模拟研究表明: DB921一端的氨基氮原子与一个水分子形成氢键, 同时, 水分子又与DNA的5位A碱基的氮原子形成一个氢键. 水分子在DB921与DNA小沟结合中起了桥连的作用, 使得直线型的芳香二脒化合物DB921通过水桥与DNA小沟结合, 水分子诱导DB921分子与DNA的小沟域构型相适应, 与DNA小沟域的AATTC碱基有较强的结合作用. 在分子水平上提供了DB921与双螺旋DNA相互作用的结构及复合物的动态变化情况, 指出水分子在DNA小沟结合二脒化合物中的识别作用, 为设计出更高生物活性的DNA小沟结合剂提供一定的理论依据.

关键词: 小沟结合, 二脒, 水分子, 分子识别

Abstract: Molecular dynamics simulations were used to investigate the interaction of DB921 with the DNA oligonucleotide d[CGCGAATTCGCG]2. A 7 ns MD calculation was performed to study the DB921-DNA complex and the results indicated that DB921 was inserted in the minor groove of DNA, binding to the region of duplex AATTC bases. A water molecule forms bifurcated pair of H-bonds between the N atom of benzimidazole ring and N3 atom of the adenine 5 in the DB921-DNA complex. This water molecule performs a key bridging role which induces a more favorable curvature configuration and matches well the DNA minor groove topology. Molecular dynamics studies complemented the structural analysis and offered a clear picture of the water-bridge, providing the theoretical guidance for the design of biologically active minor groove agents.

Key words: Minor grove binding, Diamidine, Water molecule, Molecular recognition