7th Asia-Pacific Conference on Plasma Physics, 12-17 Nov, 2023 at Port Messe Nagoya

Molecular dynamics study of DNA damage induced by hydroxyl radicalsSusumu Fujiwara1, Ryuta Kawanami2, Tomoko Mizuguchi1, Yoshiteru Yonetani3, Tsukasa Aso4,Hiroaki Nakamura5,61
Faculty of Materials Science and Engineering, Kyoto Institute of Technology, 2 Grad. School of
Science and Technology, Kyoto Institute of Technology, 3 Kansai Photon Science Institute, National
Institute of Quantum Science and Technology, 4 National Institute of Technology, Toyama College,5National Institute for Fusion Science, 6 Grad. School of Engineering, Nagoya University
e-mail (speaker): fujiwara@kit.ac.jp
DNA can be damaged by hydroxyl radicals produced incells through metabolism or radiation [1]. DNA damage
by hydroxyl radicals can be classified into two major
categories: the addition of hydroxyl radicals to the baseand the hydrogen abstraction from the sugar moiety.
Previous studies have shown that hydrogen abstraction
reactions tend to occur in the following order: C5’ > C4’> C3’ > C2’ > C1’, where C1’-C5’ represent the carbon
atoms in the sugar moiety [2]. Moreover, molecularsimulation results indicate that the differences inreactivity between DNA and hydroxyl radicals aremainly due to differences in solvent accessibility to therespective hydrogen site [3]. In this study, the hydrogen
abstraction reaction is evaluated based on theaccessibility of hydroxyl radicals.
The base sequence of DNA used is d(ATATAT) with
1783 water molecules and 8 hydroxyl radicals. The bsc1
force field of Amber22 was used for DNA and the TIP3P
force field for water. Three different models were used
for hydroxyl radicals [4-6]. Molecular dynamics (MD)simulations were performed using Amber22. The initial
box for the simulation was a truncated octahedron of45.3 Å with periodic boundary conditions. The cutoff
distance for the Lennard-Jones interaction and theelectrostatic interaction was set at 8 Å. Ten sodium ions(Na+) were added for electrical neutralization in theparticle-mesh Ewald calculation. After equilibration ofthe system, a 100 ns MD simulation was performed
under NPT conditions with an integration time step of 2fs. Temperature and pressure were set to T = 310 K and P= 1 atm, respectively. The accessibility of hydroxyl
radicals was calculated for the hydrogen of each sugar.

Figure 1.

The number of times a hydroxyl radical approachedwithin 3 Å of the hydrogen of each sugar was counted.
To efficiently sample the configuration of hydroxyl
radicals, a constraining potential with a flat bottom and aparabolic side up to 8 Å was imposed between thehydroxyl radical and the oxygen atom of the sugar
moiety.
The relationship between the number of times ahydroxyl radical approaches the hydrogen atom of eachsugar (accessibility) and the rate of hydrogen abstraction
measured in previous studies (reactivity) [2] is shown in
Fig. 1. From this figure, the number of times the oxygen
atom of the hydroxyl radical approaches the hydrogenatom, calculated as in the case of the water molecule in
the previous study [3], shows little correlation. Thissuggests that the mere proximity of a hydroxyl radical toa hydrogen atom does not necessarily result in hydrogen
abstraction.
References[1] W. K. Pogozelski and T. D. Tullius, Chem. Rev. 98,1089 (1998).
[2] B. Balasubramanian, W. K. Pogozelski, T. D. Tullius,
Proc. Natl. Acad. Sci. 95, 9738 (1998).
[3] Y. Yonetani and H. Nakagawa, Chem. Phys. Lett. 749,137441 (2020).
[4] M. G. Campo and J. R. Grigera, J. Chem. Phys. 123,084507 (2005).
[5] B. Fiser, B. Jójárt, I. G. Csizmadia, B. Viskolcz,
PLOS ONE 8, e73652 (2013).
[6] E. Lindahl, B. Hess, D. van der Spoel, Mol. Model.
Annu. 7, 306 (2001).

Relation between hydroxyl radical accessibilities to each hydrogen atom.