Influence of DNA structure on the reactivity of the guanine radical cation
Influence of DNA structure on the reactivity of the guanine radical cation
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DOI：
10.1002/chem.200400171
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发表时间：
2004-10-04
影响因子：
4.3
通讯作者：
Parrinello, M
中科院分区：
文献类型：
--
作者：
Gervasio, FL;Laio, A;Parrinello, M
通过自由基阳离子形成的DNA氧化损伤是诱变、癌症和与衰老相关的生理变化的常见原因。通过使用最先进的从头算分子动力学模拟，我们研究了指导这一过程的第一步的机制。在这里提出的机制中，鸟嘌呤，其中具有最低的氧化电位的碱基，磷酸骨架起着至关重要的作用。我们发现，速率限制步骤是水的质子化。我们阐明了当地环境在大大降低屏障中的作用。在这方面特别相关的是磷酸骨架的作用。
Oxidative damage of DNA via radical cation formation is a common cause of mutagenesis, cancer and of the physiological changes associated with aging. By using state-of-the-art ab initio molecular dynamics simulations, we study the mechanism that guides the first steps of this process. In the mechanism proposed here, guanine, which among the bases has the lowest oxidation potential, and the phosphate backbone play a crucial role. We found that the rate limiting step is the water protolysis. We illuminate the role of the local environment in considerably lowering the barrier. Of particular relevance in this respect is the role of the phosphate backbone.