多尺度QM/MM分子动力学研究溶液中羟基自由基对鸟嘌呤的损伤
Multiscale QM/MM Molecular Dynamics Study on the First Steps of Guanine-Damage by Free Hydroxyl Radicals in Solution
摘要：
了解自由OH自由基夺取氢对DNA碱基的损伤对于揭示辐射二次效应产生的羟基自由基的影响具有特别重要的意义。以前的研究解决了这个问题与截断的DNA碱基的从头计算量子模拟需要研究这样的电子自旋相关的过程是计算昂贵的。在这里，我们第一次采用多尺度和混合的量子力学-分子力学模拟研究在水的存在下，所有的水分子和脱氧核糖磷酸片段处理与简单的经典分子力学方案的OH自由基与鸟嘌呤-脱氧核糖-磷酸DNA分子单元的相互作用。我们的研究结果表明，水的存在强烈地改变了氢提取反应，因为OH自由基与水的氢键限制了OH自由基相对于DNA碱基（此处为鸟嘌呤）的相对取向。这导致化学途径中的角度各向异性和比先前预期的真空中相同系统的氢提取机制中的效率更低。该方法可以很容易地扩展到单链和双链DNA，而没有任何可观的计算成本，因为这些分子单元可以在经典子系统中处理，如这里已经证明的。
英文摘要：
Understanding the damage of DNA bases from hydrogen abstraction by free OH radicals is of particular importance to reveal the effect of hydroxyl radicals produced by the secondary effect of radiation. Previous studies address the problem with truncated DNA bases as ab-initio quantum simulation required to study such electronic spin dependent processes are computationally expensive. Here, for the first time, we employ a multiscale and hybrid Quantum-Mechanical-Molecular-Mechanical simulation to study the interaction of OH radicals with guanine-deoxyribose-phosphate DNA molecular unit in the presence of water where all the water molecules and the deoxyribose-phosphate fragment are treated with the simplistic classical Molecular-Mechanical scheme. Our result illustrates that the presence of water strongly alters the hydrogen-abstraction reaction as the hydrogen bonding of OH radicals with water restricts the relative orientation of the OH-radicals with respective to the the DNA base (here guanine). This results in an angular anisotropy in the chemical pathway and a lower efficiency in the hydrogen abstraction mechanisms than previously anticipated for identical system in vacuum. The method can easily be extended to single and double stranded DNA without any appreciable computational cost as these molecular units can be treated in the classical subsystem as has been demonstrated here.
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