Molecular dynamics simulation of clustered DNA damage site with DNA repair enzyme MutM

Higuchi, Mariko; Pinak, M.

Ionizing radiation leads to the clustered DNA damage sites, which are defined as two or more single lesions induced within 10-20 base pairs (bp). The detail mechanism of repair of cluster lesions is not known. The experimental results showed that the excision of an 8-oxo-7,8-dihydroguanine 8-oxoG lesion by glycosylase MutM is strongly inhibited by the presence of an abasic (AP) site on the opposite strand with a 1bp separation from the 8-oxoG lesion. In this study, we present the results of molecular dynamics (MD) simulation, on comparison of the single 8-oxoG damaged DNA and the cluster damaged DNA containing AP site and 8-oxoG. In order to proceed with MD simulation we have calculated the molecular properties of damaged sites using quantum chemical approach. We have found the molecular structure and atomic charge distribution differ from those of non-damaged DNA parts.