Department of Chemistry and Biochemistry, National Chung Cheng University, Taiwan.
J Phys Chem B. 2012 Sep 13;116(36):11173-9. doi: 10.1021/jp307239x. Epub 2012 Aug 31.
The ubiquitous nature and persistence of exocyclic DNA adducts suggest their involvement as initiators of carcinogenesis. We have investigated the misincorporation properties of the exocyclic DNA adduct, 3,N(4)-ethenocytosine, using DFT and DFT-D methods. Computational investigations have been carried out by using the B3LYP, M062X, and wB97XD methods with the 6-31+G* basis set to determine the hydrogen bonding strengths, binding energy, and physical parameters. The single point energy calculations have been carried out at MP2/6-311++G** on corresponding optimized geometries. The energies were compared among the 3,N(4)-ethenocytosine adduct with DNA bases to find the most stable conformer. The solvent phase calculations have also been carried out using the CPCM model. The computed reaction enthalpy values provide computational insights to the earlier experimental observation in in vitro, E.coli, and mammalian cells of a high level of substitution mutation in which C → A transversion results from εC-T pairing [εC-T3 and εC-T4] in the adduct containing DNA sequence.
外源性 DNA 加合物普遍存在且具有持久性，这表明它们可能作为致癌作用的启动子。我们使用 DFT 和 DFT-D 方法研究了外源性 DNA 加合物 3,N(4)-乙烯胞嘧啶的错配特性。通过使用 B3LYP、M062X 和 wB97XD 方法以及 6-31+G* 基组，进行了计算研究，以确定氢键强度、结合能和物理参数。在相应的优化几何结构上，使用 MP2/6-311++G** 进行单点能计算。将能量与 DNA 碱基的 3,N(4)-乙烯胞嘧啶加合物进行比较，以找到最稳定的构象。还使用 CPCM 模型进行了溶剂相计算。计算得到的反应焓值为体外、大肠杆菌和哺乳动物细胞中实验观察到的高水平取代突变提供了计算上的见解，其中 C→A 颠换是由加合物中 DNA 序列中的 εC-T 配对 [εC-T3 和 εC-T4] 引起的。
