Computer Simulation of DNA Radiation Damage

辐射对生物系统的影响一直是一个深入研究的研究领域，但仍然有许多问题和兴趣点供未来研究。辐射最重要的生物效应是对DNA造成损伤，主要是双链断裂，但我们还远未了解损伤是如何产生的，以及是什么决定了损伤。我们能够在原子水平上使用分子动力学来模拟辐射与目标分子之间的相互作用，并在极小的时间尺度上研究这些情景如何随时间演变。研究的另一部分将是调查在造成损害后分子结构如何演变。这些模拟将在宏观尺度上进行，并将更多地研究这些过程最终如何导致受损的DNA无法通过细胞修复机制有效修复，从而导致细胞死亡。将研究的关键领域将包括分子水平的模拟技术，以详细研究离子和电子对生物系统的影响，并确保这些模拟能够全面反映现实的生物条件。该项目的长期目标是模拟辐射损害过程的各个阶段。这些阶段包括：在来自入射离子束的电离反应之后产生次级反应性物质，如电子、空穴和自由基，这些次级电子和自由基通过生物介质的传输，以及在现实环境中由低能电子、离子和自由基引起的终点生物效应。现在众所周知，辐射的直接损伤不太可能是大多数DNA链断裂的来源。更有可能造成大部分损害的是环境中产生的二次反应物的间接损害。因此，需要充分了解这些反应物是什么以及它们是如何形成的。下一阶段是充分了解这些次级反应物通过生物介质的运输，即，一间牢房在低能量下，这些反应物将无法在介质中行进很远，因此任何模拟都将在短时间内完成。重要的是要知道它们如何与DNA成分相互作用，以及在每种可能的情况下，哪些成分是可行的。该项目的潜在影响可能包括改进这些相互作用模拟中使用的技术和代码，以及对如何通过放射治疗和放化疗治疗各种类型的癌症产生临床影响。通过提高DNA如何与辐射相互作用的知识，我们可以提高癌细胞如何与辐射相互作用的知识，并利用这一点来改善患者临床实践中使用的技术。该项目还可用于帮助验证以前实验和模拟的方法和结果，并确认其准确性。在研究原子粒子之间的相互作用时，可以使用各种各样的模拟模型，并且这些模型不断改进。可以研究新的和更准确的技术和想法，然后将其纳入模型中。这方面的一个例子是电子在低能量（低于10 eV）下的阻止本领。在这里，动力学的经典图像被打破，需要考虑电子交换等量子效应。目前用于模拟能量如此低的电子的模型还没有很好地定义，这一领域的知识可能会产生重要影响。这一领域的从业者将欣赏蒙特卡罗粒子轨道模拟代码（如Geant 4-DNA）的准确性的改进。

The effect of radiation on biological systems has been an intensely studied field of research but one that still that has many questions and points of interest for future investigation. The most important biological effect of radiation is to cause damage to DNA, mainly in the form of double strand breaks, but we are still far from understanding how the damage is produced and what determines it. We are able to use molecular dynamics at the atomic level to simulate the interactions between radiation and target molecules and investigate how these scenarios evolve through time on extremely small timescales. Another part of the research would be to investigate how the molecular structure evolves after the damage has been inflicted. These simulations would be on the macroscopic scale and would look more into how these processes eventually lead to damaged DNA that cannot be repaired effectively by cell repair mechanisms and which then leads to cell death. Key areas that will be researched will include simulation techniques at the molecular level to study, in detail, the effects of ions and electrons on biological systems, and to ensure that these simulations are giving a thorough representation of realistic biological conditions. The long-term goals of the project would be to simulate various stages of the radiation damage process. These stages include: the generation of secondary reactive species like electrons, holes and free radicals after ionization reactions from the incident ion beams, the transport of these secondary electrons and radicals through the biological medium and, end-point biological effects caused by low-energy electrons, ions and radicals in a realistic environment. It is now well known that direct damage from radiation is an unlikely source for the majority of breaks in the DNA strand. What is more likely to cause the majority of damage is indirect damage from secondary reactants generated in the environment. A full understanding of what these reactants are and how they are formed is therefore required. The next stage is to fully appreciate the transport of these secondary reactants through a biological medium, i.e., a cell. At low energies, these reactants will not be able to travel far through the medium so any simulations will be done over a short timescale. It is important to know how these interact with DNA components and precisely which components are viable for breakages in each possible circumstance. The potential impact for this project could range from improving on the techniques and codes used in the simulations of these interactions to having a clinical impact in how various types of cancers are treated through radiotherapy and chemoradiotherapy. By improving the knowledge of how DNA interacts with radiation, we can improve the knowledge of how cancerous cells interact with radiation and use this to improve the techniques used in clinical practice of patients. The project could be also be used to help verify the methodology and results of previous experiments and simulations and confirm their accuracy. There are a wide variety of simulation models that can be used when investigating the interactions between atomic particles and these models are continually improved. New and more accurate techniques and ideas can be investigated that can then be incorporated into the models. One example of this is the stopping power of electrons at low energies, below 10 eV. Here, the classical picture of the dynamics breaks down and quantum effects such as electron exchange needs to be considered. The models currently used in simulations for electrons with energies this low are not well defined and knowledge of this area can have an important impact. Practitioners in this field will appreciate the improvements in the accuracy of Monte Carlo particle track simulation codes such as Geant4-DNA.