Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, USA.
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Phys Rev Lett. 2023 Mar 17;130(11):118401. doi: 10.1103/PhysRevLett.130.118401.
The lack of molecular-level understanding for the electronic excitation response of DNA to charged particle radiation, such as high-energy protons, remains a fundamental scientific bottleneck in advancing proton and other ion beam cancer therapies. In particular, the dependence of different types of DNA damage on high-energy protons represents a significant knowledge void. Here we employ first-principles real-time time-dependent density functional theory simulation, using a massively parallel supercomputer, to unravel the quantum-mechanical details of the energy transfer from high-energy protons to DNA in water. The calculations reveal that protons deposit significantly more energy onto the DNA sugar-phosphate side chains than onto the nucleobases, and greater energy transfer is expected onto the DNA side chains than onto water. As a result of this electronic stopping process, highly energetic holes are generated on the DNA side chains as a source of oxidative damage.
对带电粒子辐射（如高能质子）引起的 DNA 电子激发响应缺乏分子水平的理解，仍然是推进质子和其他离子束癌症治疗的一个基本科学瓶颈。特别是，不同类型的 DNA 损伤对高能质子的依赖性代表了一个重大的知识空白。在这里，我们采用第一性原理实时含时密度泛函理论模拟，使用大规模并行超级计算机，揭示高能质子在水中传递到 DNA 的量子力学细节。计算表明，与碱基相比，质子在 DNA 糖-磷酸侧链上沉积的能量显著更多，并且预计 DNA 侧链上的能量转移大于水上的能量转移。由于这个电子阻止过程，在 DNA 侧链上产生了高能空穴，作为氧化损伤的来源。
