Influence of solvating water molecules on the attacking mechanisms of OH-radical to DNA base pairs: DFT calculations in explicit waters

Abstract

To elucidate the influence of solvating water molecules on the attacking mechanism of OH-radical to DNA base pairs (G–C and A–T), we investigated the reaction mechanism in water, by the use of the density functional theory (DFT) calculations by considering water molecules explicitly. The results reveal that OH-radical is stabilized near the NH₂ group of cytosine of G–C by the water molecules hydrogen bonded to the OH-radical and that 2.5 kcal/mol activation free energy is needed for extracting the hydrogen atom from the NH₂ group. On the other hand, OH-radical prefers to extract the hydrogen atom from the NH₂ group of adenine in the solvated A–T. As for the tautomeric reaction of the base pair attacked by OH-radical, we found the transition state for the reaction from A to T to its tautomeric form A*–T*, although the activation free energy is rather large (25 kcal/mol). By contrast, in the G–C attacked by OH-radical, one central proton can move freely from G to C, resulting in the tautomeric form G*–C*. Therefore, our DFT calculations in explicit water molecules elucidate the possibility that the attacking of OH-radical to G–C causes its tautomeric form G*–C*, while A–T attacked by OH-radical cannot transform into its A*–T* form in a normal condition. This finding will be useful for predicting the effect of OH-radical on the genetic information recorded in DNA base sequences.