化学学报 ›› 2014, Vol. 72 ›› Issue (8): 956-962.DOI: 10.6023/A14040238 上一篇    下一篇

研究论文

7,8-二氢-8-氧鸟嘌呤碱基对的量子化学研究

张千慧, 王阳, 刘翠, 杨忠志   

  1. 辽宁师范大学化学化工学院 大连 116029
  • 收稿日期:2014-04-01 出版日期:2014-08-14 发布日期:2014-05-29
  • 通讯作者: 刘翠, 杨忠志 E-mail:liuc@lnnu.edu.cn;zzyang@lnnu.edu.cn
  • 基金资助:

    项目受国家自然科学基金重点(No. 21133005)资助.

Investigation of Base Pairs Containing 7,8-Dihydro-8-oxoguanine by Quantum Chemistry

Zhang Qianhui, Wang Yang, Liu Cui, Yang Zhongzhi   

  1. School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029
  • Received:2014-04-01 Online:2014-08-14 Published:2014-05-29
  • Supported by:

    Project supported by the National Basic Research Program of China (No. 21133005).

遗传信息的完整性不断受氧化基因的威胁,7,8-二氢-8-氧鸟嘌呤(8-oxo-G)是氧化DNA损伤最常见的产物. 氧化碱基会引起基因突变、癌变及衰老等. 应用量子化学方法分析得出:鸟嘌呤(G)被氧化为8-oxo-G后,其电荷分布、氢键的供体和受体位点的数目和位置随之改变,N7和O6原子所带的电荷变得更负,使得它们作为氢键供体的能力增强. 从而G被误认为其他碱基,与正常碱基形成多种氢键复合物. 可将8-oxo-G划分为3个作用位点与正常碱基相互作用. 与正常的单体相比,碱基对中形成氢键的受体原子上所带电荷平均变负0.05e,占原电荷的8%; 供体H原子所带电荷平均变正0.02e,占原电荷的4%. 1位点与正常碱基作用形成的氢键复合物更稳定,2位点和3位点性质相似,水溶剂使碱基对的结合能力减弱,其中与C作用形成氢键复合物的结合能减弱程度最大,且使碱基对结合能力的次序改变. 在8-oxo-G导致的GC→TA突变中,亲核反应位点从G所在链转到A(C)所在链,影响酶对碱基的识别,从而产生基因突变.

关键词: 从头算方法, 氧化碱基对, 氢键, 电荷分布, 能量

The integrity of the genetic information is constantly threatened by oxidized agents. 7,8-Dihydro-8-oxoguanine (8-oxo-G) is the most common form of oxidative DNA damage. The accumulation of oxidized bases has associated with numerous diseases and cancers. The properties of oxidized base pairs containing 8-oxo-G were investigated by quantum mechanics methods. In this paper all model molecular structures were optimized by B3LYP/6-31+G* method, the frequency calculations are carried out to confirm that all the structures obtained are geometrically stable. The energies were determined at the MP2/aug-cc-pVDZ level with basis set superposition error corrections and the molecular orbital diagrams were obtained at HF/STO-3G level. The calculation results show that when guanine (G) is oxidized to 8-oxo-G, the charge distribution, site number and location of H-bond donor and accepter have been changed. Oxidation on C8 of G has the most influence on the partial charge of N7 and O6, which enhances their ability as H-bond donor. Then, G is misread as other bases to form varied H-bonding compounds with canonical bases. 8-oxo-G has three sites to pair with other bases. Compared with canonical bases, the partial charge of proton acceptors in H-bond complexes increased by 0.05e averagely, which is 8% of the original charge; the partial charges for proton donors have a decrease of 0.02e, which is 4% of the original charge. The calculation results of binding energy and second-order stabilization energy show that the hydrogen-bonded complexes formed at site 1 are more stable. The sites 2 and 3 have similar properties. Only 8-oxo-G1:C (WC) has three hydrogen bonds and its binding energy is the closest to that of G:C in all the oxidized base pairs. The binding energies of base pairs have been weakened by solution, where the complexes pairs with C have been significantly reduced. And the order of the binding energy has been changed. From the HOMO and LUMO, we can come out that the HOMOs of all the oxidized base pairs are on 8-oxo-G, which is the same as G:C, and LUMOs have no good rules. In the GC→TA transition induced by 8-oxo-G, the nucleophilic reaction site will transfer from the strand containing G to the other strand containing A(C). This will affect the recognition by the enzyme, and lead to genetic mutations.

Key words: ab initio, oxidized base pairs, hydrogen bond, charge population, energy