Jorge Kohanoff

  • Can low-energy electrons produce DNA strand breaks?

    Jorge Kohanoff1, Maeve McAllister1, Maeve Smyth1, Gareth Tribello1, Amy Williamson1, Lila Boüessel du Bourg1,2, Alberto Fraile1,3, Bin Gu1,4, and Ilya Fabrikant5

    1Atomistic Simulation Centre, Queen’s University Belfast, Northern Ireland, UK
    2 Department of Chemistry, Ecole Normale Supérieur, Paris, France
    3 CCQCN, Department of Physics, University of Crete, Heraklion, Greece
    4 Department of Physics, NUIST, Nanjing, China
    5 Department of Physics and Astronomy, University of Nebraska-Lincoln, NE, USA

    DNA damage caused by irradiation has been studied for many decades. Motivations include assessing the dangers posed by radiation, and understanding how to improve its efficiency in combating cancer. Since the seminal work of Sanche and co-workers [1], low-energy secondary electrons produced by ionization became an important player in the field, together with free radicals. In this presentation I will describe a research programme we are conducting with the goal of understanding, via computer simulation, the role of low-energy electrons in the behaviour of DNA components in a realistic, physiological-like environment.

    Firstly, we conducted R-matrix calculations for microsolvated nucleobases, which showed an enhancement of the dissociative electron attachment (DEA) cross section [2]. We then ran first-principles molecular dynamics (FPMD) simulations using initial conditions drawn from the DEA distribution, observing interesting differences between gas-phase, microsolvated and fully solvated environments. We then examined the role of excess electrons in the dynamics and thermodynamics of increasingly complex solvated DNA models, from bases to polynucleotides. Dynamical simulations after vertical attachment show a fast localization of the excess electron from a pre-solvated state to a valence bound orbital [3], while in polynucleotides they exhibit a rich pattern of localization and fluctuation between the various bases, which depends on the sequence. The protective role of histones in chromatin was addressed by simulating nucleobases in glycine. Free energy barriers for phosphodiester bond cleavage were calculated by means of constrained FPMD. Barriers of the order of 5-10 kcal/mol suggest that this is a regular feature at 300K [4]. The competition between bond cleavage and protonation was also studied by constrained MD, while the effects of sequencing on bond breaks in polynucleotides were addressed using metadynamics. Finally, we conducted simulations of shock waves in solvated nucleotides, in a first attempt to assess, from first-principles, the role of thermo-mechanical effects due to ion irradiation.

    [1] B. Boudaiffa, P. Cloutier, D. Hunting, M.A. Huels, and L. Sanche. “Resonant formation of DNA strand breaks by extremely low energy (3-20 eV) electrons”, Science 287, 1658 (2000).
    [2] M. Smyth, J. Kohanoff and I. I. Fabrikant, “Electron induced hydrogen loss in uracil in a water cluster environment”, submitted to J. Chem. Phys.
    [3] M. Smyth and J. Kohanoff, “Excess Electron Localization in Solvated DNA Bases”, Phys. Rev. Lett. 106, 238108 (2011).
    [4] M. Smyth and J. Kohanoff, “Excess Electron Interactions with Solvated DNA Nucleotides: Strand Breaks Possible at Room Temperature”, J. Am. Chem. Soc. 134, 9122 (2012).