Attacking mechanism of hydroxyl radical to DNA base-pair: density functional study in vacuum and in water.
Recently, the influence of radiation on human body has been recognized as a serious problem. In particular, highly reactive hydroxyl radicals *OH produced by the radiation react with DNA, resulting in a great damage on its structure and electronic properties. It is thus important to investigate the reaction mechanism of *OH to DNA for elucidating the initial damage in DNA induced by the radiation. In the present study, we search for transition states (TS) of the reaction between G-C/A-T base-pair and [Formula: see text] in vacuum and in water, by the density functional theory (DFT) calculations. At first, we obtain the stable structures for the dehydrogenated G-C and A-T, in which the hydrogen atom of NH2 group of G or A base is abstracted by [Formula: see text]. From the structures of the dehydrogenated as well as the natural base-pairs, the TS between these structures is searched for and the activation free energy (AFE) is estimated for the reaction. In vacuum, AFEs for the G-C and A-T are almost the same each other, while the stabilization energy by the reaction for G-C is about 4.9 kcal/mol larger than that for A-T, indicating that the population of the dehydrogenated G-C is remarkably larger than that of the dehydrogenated A-T in vacuum. On the other hand, in water approximated by the continuum solvation model, the AFE for A-T is 2.6 kcal/mol smaller than that for G-C, indicating that the reaction dehydrogenated by [Formula: see text] occurs more frequently for the solvated A-T base-pair than G-C.
a Department of Computer Science and Engineering , Toyohashi University of Technology , Tempaku-cho, Toyohashi, Aichi 441 8580 , Japan.
Eisuke
E
Shimizu
Yuki
Y
Tokuyama
Naoko
N
Okutsu
Kazuya
K
Nomura
Victor I
VI
Danilov
Noriyuki
N
Kurita
D020029:Base Pairing / Q000235:genetics / Q000528:radiation effects*; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004249:DNA Damage; D006801:Humans; D006860:Hydrogen Bonding; D017665:Hydroxyl Radical / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D009690:Nucleic Acid Conformation / Q000528:radiation effects; D013816:Thermodynamics; D014618:Vacuum; D014867:Water / Q000737:chemistry*
D014867:Water; D017665:Hydroxyl Radical; D004247:DNA
DNA base-pair; ab initio calculation; density functional theory; hydroxyl radical; reaction mechanism; transition states