CEISAM UMR CNRS, Université de Nantes, France.
Chemphyschem. 2011 Oct 4;12(14):2615-23. doi: 10.1002/cphc.201100264. Epub 2011 Aug 24.
Metallic ions are essential for stabilizing the nucleic acid structure, and are also involved in the majority of RNA and DNA biological functions. However, at large concentrations metals may play an opposite role by promoting alterations in the genetic code (mutagenicity). To contribute to the understanding of this effect, theoretical tools are used to investigate the influence of the magnesium dication on the guanine-cytosine (GC) base pair structure and stability. To this end, a fully hydrated Mg(2+) cation is inserted in two models: an isolated GC base pair, and a more realistic DNA model corresponding to a hydrated double-stranded trimer. Calculations performed with a hybrid ONIOM approach reveal that the Mg(2+) cation coordination to the GC base pair alters drastically the natural tautomeric equilibria in DNA by promoting single proton transfer. Nevertheless, the generated rare tautomer will have a limited impact on the total spontaneous mutation due to the low back-reaction barrier allowing a quick return to the canonical form. Additionally, it is demonstrated that the major effects of biological environment arise from the hydration and stacking influence, whereas the impact of phosphate groups is minor.
金属离子对于稳定核酸结构是必不可少的，并且还参与了大多数 RNA 和 DNA 的生物功能。然而，在较大浓度下，金属可能会通过促进遗传密码的改变（致突变性）而起到相反的作用。为了帮助理解这种影响，理论工具被用于研究二价镁离子对鸟嘌呤-胞嘧啶（GC）碱基对结构和稳定性的影响。为此，在两个模型中插入了完全水合的 Mg(2+)阳离子：一个孤立的 GC 碱基对，和一个更现实的对应于水合双链三聚体的 DNA 模型。使用混合 ONIOM 方法进行的计算表明，Mg(2+)阳离子与 GC 碱基对的配位通过促进单质子转移，极大地改变了 DNA 中的自然互变异构平衡。然而，由于存在较低的反向反应壁垒，允许快速回到规范形式，因此产生的稀有互变异构体对总自发突变的影响将是有限的。此外，还证明了生物环境的主要影响来自于水合和堆积的影响，而磷酸基团的影响较小。
