Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, Campinas 13083-859, SP, Brazil.
Instituto de Química, Universidade Estadual de Campinas, Campinas 13083-970, SP, Brazil.
Int J Mol Sci. 2022 Sep 2;23(17):10007. doi: 10.3390/ijms231710007.
Heavy charged particles induce severe damage in DNA, which is a radiobiological advantage when treating radioresistant tumors. However, these particles can also induce cancer in humans exposed to them, such as astronauts in space missions. This damage can be directly induced by the radiation or indirectly by the attack of free radicals mainly produced by water radiolysis. We previously studied the impact of a proton on a DNA base pair, using the Time Dependent-Density Functional Theory (TD-DFT). In this work, we go a step further and study the attack of the OH· radical on the Guanine nucleotide to unveil how this molecule subsequently dissociates. The OH· attack on the H1', H2', H3', and H5' atoms in the guanine was investigated using the Ehrenfest dynamics within the TD-DFT framework. In all cases, the hydrogen abstraction succeeded, and the subsequent base pair dissociation was observed. The DNA dissociates in three major fragments: the phosphate group, the deoxyribose sugar, and the nitrogenous base, with slight differences, no matter which hydrogen atom was attacked. Hydrogen abstraction occurs at about 6 fs, and the nucleotide dissociation at about 100 fs, which agrees with our previous result for the direct proton impact on the DNA. These calculations may be a reference for adjusting reactive force fields so that more complex DNA structures can be studied using classical molecular dynamics, including both direct and indirect DNA damage.
重带电粒子在 DNA 中诱导严重损伤，这在治疗耐辐射肿瘤时是一种放射生物学优势。然而，这些粒子也会在接触它们的人类中引发癌症，例如太空任务中的宇航员。这种损伤可以直接由辐射诱导，也可以由水辐射分解主要产生的自由基的攻击间接诱导。我们之前使用时间相关密度泛函理论 (TD-DFT) 研究了质子对 DNA 碱基对的影响。在这项工作中，我们更进一步，研究了 OH·自由基对鸟嘌呤核苷酸的攻击，以揭示该分子随后如何解离。使用 Ehrenfest 动力学在 TD-DFT 框架内研究了 OH·在鸟嘌呤中的 H1'、H2'、H3'和 H5'原子上的攻击。在所有情况下，氢提取都成功了，随后观察到碱基对解离。DNA 会解离成三个主要片段：磷酸基团、脱氧核糖糖和含氮碱基，无论攻击哪个氢原子，差异都很小。氢提取发生在大约 6 fs，核苷酸解离发生在大约 100 fs，这与我们之前关于直接质子撞击 DNA 的结果一致。这些计算结果可能为调整反应力场提供参考，以便使用经典分子动力学研究更复杂的 DNA 结构，包括直接和间接的 DNA 损伤。
