Proton cancer therapy (PCT) uses high-energy protons to kill cancerous tumors with minimum damage on
healthy tissues and without the side effects of X-ray therapy. Colliding protons induce cell water radiolysis
reactions that generate reactive species: ions, electrons and radicals. Those species damage the DNA of
cancerous cells, prompting their apoptosis. Despite established clinical use, the microscopic details of PCT
reactions remain elusive. That has prevented a rational design of PCT that can maximize its therapeutic power
and minimize its side effects. This poor characterization of PCT is due to the fact that even the most advanced
experimental/clinical techniques cannot completely reveal the microscopic details of PCT, especially without
harming human subjects. To overcome this situation, we are conducting computer simulations of PCT reactions
with novel quantum-dynamics methods. Thus, dangerous PCT reactions that cannot be safely tested in the
human body are innocuously run on computers at a very low cost. Our proposed quantum-dynamics methods
are based on the electron nuclear dynamics (END) theory —a time-dependent, variational, on-the-fly and non-
adiabatic method— implemented in our parallel code PACE. We will study three main types of PCT reactions:
(1) PCT water radiolysis reactions—the fundamental PCT reactions in cell water that produce the ions, electrons
and radicals that damage cellular DNA; (2) proton-induced DNA damage and (3) electron-induced DNA damage.
For (3), we will verify Simons' mechanism for electron-induced DNA damage (electron capture in a DNA base,
transfer through sugar, and single strand break at the phospho-ester bond) and other competing mechanisms
revealed by recent DNA experiments. We are the first performing time-dependent, non-adiabatic simulations of
large nucleotide samples for reactions (2) and (3). Our studies will provide results not obtained before by other
computer simulations and experiments, such as the precise determination of the mechanisms of PCT reactions
and the accurate prediction of reactions integral cross sections. Those cross sections are the needed input data
to design Monte Carlo (MC) codes used for radiation dosimetry, radiotherapy sessions, radioprotection protocols
and medical imaging (the team of the MC code TILDA-V has paid attention to some of our results in their designs).
Thus, our studies are making a positive impact on PCT research and therapeutics and on other areas of ion-
induced DNA damage research such as non-cancerous radiotherapy, studies of mutagenesis, ageing, etc. We
will use both existing and new END methods. Existing methods are the simplest-level END and our END/Kohn-
Sham Density Functional Theory that includes electron correlation effects. Both methods adopt nuclear classical
mechanics and an electronic single-determinantal wavefunction. New methods to be developed with this grant
are END with the continuum polarizable model, to describe the solvation effects on PCT reactions by cell bulk
water, and END with plane waves, to accurately describe scattering/capture of unbound electrons from water/to
DNA. With these new methods, PACE will become a more accurate and versatile tool to describe PCT processes.