Review and Strategy for Implementing Criteria of DNA Damage in an Atomistic Model using Geant4-DNA

Our project has been developing a Monte Carlo simulation tool using Geant4-DNA for assessing radiation-induced DNA damage in the atomic level. Radiation damage consists of direct effects caused by direct energy transfer from charged particles, and indirect effects starting from hydrogen abstraction reactions by OH radicals through water radiolysis. These effets induce damages in the atomic structure of DNA molecules. We have introduced molecular structures from the Protein Data Bank database into our simulations to evaluate DNA strand breaks by both direct and indirect effects. For the indirect effect, we employed a mechanical approach to determine damage sites at the atomic level by examining the correlation between post-diffusion coordinates of OH radicals after an average reaction time and the atoms in the DNA molecules. The results showed that the portion of strand breaks correlates with experimental data [1]. In addition, we evaluated the activation energy for hydrogen abstraction reactions using the semi-empirical quantum chemical calculation program MOPAC and assessed the accessibility of OH radicals to DNA molecule hydrogen using the molecular dynamics simulation program Amber. These results illustrate that the proportion of strand breaks’ sites can be explained from a chemical reaction process [2]. Meanwhile, it is desirable to incorporate the results from these quantum chemical and molecular dynamics calculations into the Monte Carlo simulation. This presentation reports on our strategy to implement the DNA damage models to utilize the parameters achieved from the quantum chemical and molecular dynamics calculations.