Analyzing hydroxyl radical accessibility related to hydrogen abstraction in a DNA sugar moiety using molecular dynamics simulations

Exposure of water to ionizing radiation induces OH radical formation. Within cellular environments, the presence of OH radicals can stimulate the abstraction of hydrogen atoms from the sugar backbone of DNA. Subsequent damage to DNA structures leads to various diseases. Multiple studies have elucidated this phenomenon, especially computational studies examining the differences in the degree of abstraction between the sugar hydrogens (H1′, H2′, H2″, H3′, H4′, H5′, and H5″). However, the details of this phenomenon have not yet been clarified. It is rare for OH radicals to approach DNA within the simulation time, making it difficult to adequately sample the configurations in which OH radicals immediately precede the abstraction of the hydrogen atoms. To address this problem, we performed molecular dynamics simulation to calculate the relative accessibility by putting a potential on nucleotides and OH radicals. As a result, we found that the accessibility of OH radicals to each hydrogen atom differs from that of water molecules as solvents. A more detailed accessibility analysis revealed that the angle of the OH radicals approaching the hydrogen atoms of ribose and the energy barrier for abstracting the hydrogen atoms can be considered to improve the correspondence with the experimental data. Moreover, we found that the behavior of water molecules and OH radicals toward accessibility to DNA differs significantly and showed that the factors are related to the physicochemical properties of water molecules and OH radicals, as well as the structure of DNA.