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化学学报
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化学学报 ›› 2010, Vol. 68 ›› Issue (16): 1553-1560.    下一篇

研究论文

6-烷基鸟嘌呤与DNA碱基间氢键作用的理论研究

林雪飞，孙成科，姚立峰，陈益山，杨思娅   

  1. (曲靖师范学院化学与化工学院 曲靖 655000)
  • 投稿日期:2010-03-01 修回日期:2010-04-18 发布日期:2010-05-31
  • 通讯作者: 杨思娅 E-mail:yangsiyall@163.com
  • 基金资助:

    DNA碱基烷基化与乳腺癌BRCA1基因启动子区甲基化的分子模拟研究

Theoretical Studies of the Hydrogen-bond Interactions between O6-Alkylguanine and DNA Bases

LIN Xue-Fei, SUN Cheng-Ke, YAO Li-Feng, CHEN Yi-Shan, YANG Si-Ya   

  1. (School of Chemistry & Chemical Engineering, Qujing Normal University, Qujing 655000)
  • Received:2010-03-01 Revised:2010-04-18 Published:2010-05-31

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1586

被引次数

11 | 2

用密度泛函B3LYP方法在6-311＋G**基组水平上对鸟嘌呤及顺(cis-)、反式(anti-)-6-烷基鸟嘌呤(O6-AlkylG)与DNA碱基(胸腺嘧啶T、胞嘧啶C、腺嘌呤A、鸟嘌呤G)的氢键二聚体结构进行了优化. 在MP2/cc-pVXZ(X＝D,T)// B3LYP/6-311＋G**水平上, 采用完全基组外推方法校正了氢键二聚体的相互作用能, 并用完全均衡校正法(CP)校正了基组重叠误差(BSSE). 在B3LYP/6-311＋G**水平上计算了各氢键碱基对的全电子波函数, 并用分子中的原子理论(AIM)分析了碱基间的弱相互作用. 计算结果显示, 鸟嘌呤6-O烷基化改变了碱基间的氢键作用模式, 使碱基对发生了明显的螺旋桨式扭转和不同程度的位移, 碱基间的电子密度分布和氢键作用能明显减小. O6-AlkylG对DNA碱基间的氢键作用是去稳定化的, 去稳定化影响的顺序为GC＞GG＞GA≈GT. 计算结果与文献给出的实验结论基本一致.

关键词: 鸟嘌呤, 烷基化, DNA碱基, 氢键, 分子中原子理论(AIM)

The geometries of hydrogen-bond dimers between DNA bases (adenine, thymine, guanine and cytosine) and guanine, cis-O6-alkylguanine and trans-O6-alkylguanine have been optimized at the B3LYP/6-311＋G** level. The complete basis-set extrapolation method was employed at the MP2/ cc-pVXZ(X＝D,T)//B3LYP/6-311＋G** levels in order to obtain more accurate interaction energies. Counterpoise correction (CP) scheme was also used to take into account of basis set superposition error (BSSE). The all-electron wave functions of these dimers were calculated at the B3LYP/6-311＋G** level and the weak interactions were analyzed by atoms in molecules (AIM) method. The calculation results show that the alkylation of O6-guanine can lead to changes of hydrogen-bond interactions between DNA base-pairs, which results in propeller torsions and various displacements between two bases. Furthermore, the obvious decreases in interaction energies and electron densities of base-pair can also be attributed to the alkylation of guanine. Evidently, the alkylation of O6-guanine destabilizes the hydrogen-bond interactions of DNA base-pairs, and the destabilization effect decreases in the order of GC＞GG＞GA≈GT. Our calculation results are basically in agreement with the experiments.

Key words: guanine, alkylation, DNA bases, hydrogen-bond, atom in molecule (AIM)