Computer Simulation of DNA Radiation Damage

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.