Institució Catalana de Recerca i Estudis Avançats, Barcelona 08010, Spain.
Phys Chem Chem Phys. 2009 Dec 7;11(45):10608-13. doi: 10.1039/b910690a. Epub 2009 Aug 5.
Trapping of an electron by DNA leads to the formation of radical anion states of pyrimidine bases. Because these states play an important role in biological and chemical processes, their computational treatment is of particular interest. We show that simple electrostatic and quantum chemical models can accurately reproduce the adiabatic electron affinities (EAs) of short DNA stacks recently derived from high-level ab initio calculations (M. Kobylecka, J. Leszczynski, and J. Rak, J. Am. Chem. Soc., 2008, 130, 15683). The electrostatic interaction of an excess electron localized on cytosine or thymine with intra- and inter-strand adjacent nucleobases is found to strongly affect the energy of the radical anions. This interaction is the main origin of the dependence of EA of nucleobases on the nature of neighboring base pairs. In particular, the states XT(-)Y and XC(-)Y, where X and Y = C, T, are, by ca. 0.7 eV, more stable than radical anions GT(-)G and GC(-)G. We find that second-neighbor effects can also significantly modulate EAs, although being smaller than the effects of adjacent bases. The strongest destabilizing effect is found for 5'-GC and 3'-GC, while the 5'-AT base pair stabilizes the radical anion states. Using a combined QM/MD approach, we consider how structural fluctuations of DNA influence the stability of the radical anion states. Despite large dispersions of the stabilization energies due to conformational dynamics of DNA, there are only few thermally accessible structures where GT(-)G and GC(-)G are energetically more favorable than the corresponding pyrimidine triplets. Although stabilization energies calculated for stacks of regular structure are in qualitative agreement with the QM/MD results, structural fluctuations of pi stacks should be taken into account for more accurate description of the excess electron trapped by DNA. The results obtained in this study suggest that simple electrostatic models, in combination with MD simulations, can be very helpful to explore the long time scale behavior of radical anions in DNA.
DNA 捕获电子会导致嘧啶碱基的自由基阴离子态的形成。由于这些状态在生物和化学过程中起着重要作用，因此它们的计算处理特别有趣。我们表明，简单的静电和量子化学模型可以准确地再现最近从高水平从头算计算得出的短 DNA 堆积的绝热电子亲和能 (EA) (M. Kobylecka、J. Leszczynski 和 J. Rak，J. Am. Chem. Soc.，2008，130，15683)。发现局域在胞嘧啶或胸腺嘧啶上的多余电子与链内和链间相邻碱基的静电相互作用强烈影响自由基阴离子的能量。这种相互作用是 EA 随相邻碱基对性质变化的主要原因。特别是，状态 XT(-)Y 和 XC(-)Y，其中 X 和 Y = C，T，比自由基阴离子 GT(-)G 和 GC(-)G 稳定约 0.7 eV。我们发现，第二邻效应也可以显著调节 EA，尽管小于相邻碱基的效应。对于 5'-GC 和 3'-GC，发现了最强的去稳定效应，而 5'-AT 碱基对稳定了自由基阴离子态。使用 QM/MD 组合方法，我们考虑了 DNA 结构的波动如何影响自由基阴离子态的稳定性。尽管 DNA 构象动力学导致稳定能的分散很大，但只有少数热力学上可访问的结构中，GT(-)G 和 GC(-)G 在能量上比相应的嘧啶三联体更有利。尽管对于规则结构的堆积，计算得到的稳定能与 QM/MD 结果定性一致，但应该考虑π堆积的结构波动，以更准确地描述 DNA 中捕获的多余电子。本研究的结果表明，简单的静电模型与 MD 模拟相结合，可以非常有助于探索 DNA 中自由基阴离子的长时间尺度行为。
