论文标题
闪光超高剂量速率放射疗法中的氧耗竭：分子动力学模拟
Oxygen depletion in FLASH ultra-high-dose-rate radiotherapy: A molecular dynamics simulation
论文作者
论文摘要
我们提出了第一原理分子动力学（MD）模拟，并根据氧耗尽假设的机制阐述，以解释在超高剂量速率（UHDR）闪光放射疗法中观察到的正常组织损伤的缓解。我们在装有H $ _2 $ O和O $ _2 $分子的模拟盒中模拟了DNA（还代表其他生物分子（例如RNA和蛋白））的损伤。使用Monte Carlo Track结构代码Geant4-DNA模拟了Attsonds物理相互作用（电离，电子和振动激发）。电离后，{\ it i ab intio} CAR-Parrinello分子动力学（CPMD）模拟用于识别DNA-分子周围周围的H $ _2 $ O和O $ _2 $ _2 $分子转换为活性氧（ROS）。随后，通过与反应力场（ReaxFF）使用MD模拟ROS的FEMTO-temto-second反应，以说明ROS合并为新型非反应性氧（NROS），这是由于ROS之间的强耦合而导致的。时间依赖性的分子模拟揭示了在UHDR产生的ROS中形成亚稳态和瞬态意大利面条样复合物。在UHDR下产生的较高的ROS密度下，链链（即NROS）是通过有吸引力的电极性力，氢键和磁性偶极 - 偶极相互作用而介导的。 NROS往往比细胞生物分子的流动性较小，而与传统剂量率（CDR）产生的分离且稀疏的密度ROS相反。我们将这种影响归因于抑制每个颗粒轨迹引起的生物分子损伤。在给定的氧气水平下，随着剂量速率的增加，NROS链的大小和数量增加，有毒ROS成分的种群降低。
We present a first-principles molecular dynamics (MD) simulation and expound upon a mechanism of oxygen depletion hypothesis to explain the mitigation of normal tissue injury observed in ultra-high-dose-rate (UHDR) FLASH radiotherapy. We simulated damage to a segment of DNA (also representing other bio-molecules such as RNA and proteins) in a simulation box filled with H$_2$O and O$_2$ molecules. Attoseconds physical interactions (ionizations, electronic and vibrational excitations) were simulated by using the Monte Carlo track structure code Geant4-DNA. Immediately after ionization, {\it ab initio} Car-Parrinello molecular dynamics (CPMD) simulation was used to identify which H$_2$O and O$_2$ molecules surrounding the DNA-molecule were converted into reactive oxygen species (ROS). Subsequently, the femto- to nano-second reactions of ROS were simulated by using MD with Reactive Force Field (ReaxFF), to illustrate ROS merging into new types of non-reactive oxygen species (NROS) due to strong coupling among ROS. Time-dependent molecular simulations revealed the formation of metastable and transient spaghetti-like complexes among ROS generated at UHDR. At the higher ROS densities produced under UHDR, stranded chains (i.e., NROS) are produced, mediated through attractive electric polarity forces, hydrogen bonds, and magnetic dipole-dipole interactions among hydroxyl (\ce{^{.}OH}) radicals. NROS tend to be less mobile than cellular biomolecules as opposed to the isolated and sparsely dense ROS generated at conventional dose rates (CDR). We attribute this effect to the suppression of bio-molecular damage induced per particle track. At a given oxygen level, as the dose rate increases, the size and number of NROS chains increase, and correspondingly the population of toxic ROS components decreases.
