  The lack of molecular-level understanding for the electronic excitation
response of DNA to charged particle radiation, such as high-energy protons,
remains a fundamental scientific bottleneck in advancing proton and other ion
beam cancer therapies. In particular, the dependence of different types of DNA
damage on high-energy protons represents a significant knowledge void. Here we
employ first-principles real-time time-dependent density functional theory
simulation, using a massively-parallel supercomputer, to unravel the
quantum-mechanical details of the energy transfer from high-energy protons to
DNA in water. The calculations reveal that protons deposit significantly more
energy onto the DNA sugar-phosphate side chains than onto the nucleobases, and
greater energy transfer is expected onto the DNA side chains than onto water.
As a result of this electronic stopping process, highly energetic holes are
generated on the DNA side chains as a source of oxidative damage.
