Lind Maria C, Richardson Nancy A, Wheeler Steven E, Schaefer Henry F
Center for Computational Chemistry, University of Georgia, Athens, Georgia 30602, USA.
J Phys Chem B. 2007 May 17;111(19):5525-30. doi: 10.1021/jp0714926. Epub 2007 Apr 26.
The formation of radicals on DNA bases through various pathways can lead to harmful structural alterations. Such processes are of interest for preventing alteration of healthy DNA and, conversely, to develop more refined methods for inhibiting the replication of unwanted mutagenic DNA. In the present work, we explore theoretically the energetic and structural properties of the nine possible neutral radicals formed via hydrogen abstraction from the adenine-thymine base pair. The lowest energy radical is formed by loss of a hydrogen atom from the methyl group of thymine. The next lowest energy radicals, lying 8 and 9 kcal mol-1 higher than the global minimum, are those in which hydrogens are removed from the two nitrogens that would join the base pair to 2-deoxyribose in double-stranded DNA. The other six radicals lie between 16 and 32 kcal mol-1 higher in energy. Unlike the guanine-cytosine base pair, adenine-thymine (A-T) exhibits only minor structural changes upon hydrogen abstraction, with all A-T derived radicals maintaining planarity. Moreover, the energetic ordering for the radicals of the two isolated bases (adenine and thymine) is preserved upon formation of the base pair, though with a wider spread of energies. Even more significantly, the energetic interleaving of the (A-H)-T and A-(T-H) radicals is correctly predicted from the X-H bond dissociation energies of the isolated adenine and thymine. This suggests that the addition of the hydrogen-bonded complement base only marginally affects the bond energies.
通过各种途径在DNA碱基上形成自由基会导致有害的结构改变。此类过程对于防止健康DNA的改变具有重要意义，反之，对于开发更精确的方法来抑制有害诱变DNA的复制也很重要。在本工作中，我们从理论上探索了通过从腺嘌呤-胸腺嘧啶碱基对中提取氢而形成的九种可能的中性自由基的能量和结构性质。能量最低的自由基是由胸腺嘧啶甲基上的一个氢原子失去形成的。能量次低的自由基比全局最小值高8和9千卡/摩尔，是那些氢从双链DNA中连接碱基对与2-脱氧核糖的两个氮原子上被去除的自由基。其他六个自由基的能量则高出16至32千卡/摩尔。与鸟嘌呤-胞嘧啶碱基对不同，腺嘌呤-胸腺嘧啶（A-T）在氢提取后仅表现出微小的结构变化，所有源自A-T的自由基都保持平面性。此外，两个孤立碱基（腺嘌呤和胸腺嘧啶）自由基的能量排序在碱基对形成后得以保留，尽管能量分布更宽。更显著的是，从孤立腺嘌呤和胸腺嘧啶的X-H键解离能可以正确预测（A-H）*-T和A-（T-H）*自由基的能量交错。这表明氢键互补碱基的添加仅对键能产生轻微影响。
