“molecularDNA” – a Geant4-DNA example application for simulation of radiation-induced DNA damage

There is a large interest and effort in the scientific community worldwide to develop accurate models and validate radiobiological measurements of DNA damage in cells induced by hadronic particles. There have been several Monte Carlo Track Structure software codes (MCTS) developed for these purposes, making use of a bottom-up approach, starting from an early-DNA scale event to the macroscopic radiobiological endpoints such as cell survival, single and double DNA breaks, DNA repair, and other late effects. The Geant4-DNA extension (https://geant4-dna.org/) of the Geant4 (GEometry ANd Tracking) toolkit represents the first open-source and general-purpose MCTS code. Geant4-DNA delivers the framework for simulating the physical interaction of radiation with DNA molecules and the chemical stages of the water radiolysis responsible for producing oxidative radical species. It also provides validated geometrical models of cell nuclei with a complete DNA genome implemented. The geometries of cell nuclei are, by default, seeded from a fractal packing using the “fractalDNA” model, where the DNA chain is represented with a continuous Hilbert curve made of straight and turned chromatin sections, including nucleosomes. More recently, a new model of cell nuclei named the “complexDNA” has been created, incorporating all 23 chromosome pairs of a human cell. The chromosomal model showed minimal discrepancies in DNA damage yield compared to the default human cell model and demonstrated approximately three times reduction in computation time to obtain equivalent results. The geometric models are interfaced with the direct and indirect stages of DNA damage induction, and the full chain application, named “molecularDNA”, has been released as an advanced example of the Geant4-DNA toolkit in December 2022 (https://moleculardna.org). The “molecularDNA” application is user-friendly and can be utilized following simple macro commands. The first Monte Carlo study of two cancer cells, the lung carcinoma HTB-177 and the breast adenocarcinoma MCF-7, irradiated with a clinical helium ion beam using “molecularDNA” and its comparison to experimental data was published in 2023, showing good predictability of the Geant4-DNA example application. An overview of the “molecularDNA” application, with its design, purpose, and features, will be presented in this talk, as well as a demonstration of its predictability compared to experimental data of cancer cells irradiated with helium ions. The new computational technique to create complex chromosomal DNA geometries will also be detailed.