Molecular dynamics simulation of 7,8-dihydro-8-oxoguanine DNA

摘要

To elucidate the effect of guanine lesion produced by the oxidative damage on DNA, 1 nanosecond molecular dynamics simulations of native and oxidized DNA were performed. The target DNA molecules are dodecamer duplex d(CGCGAATTCGCG)_2 and its derivative duplex d (C_1G_2C_3(8-oxoG) _4A_5A_6T_7T_8C_9G_(10)C_(11)G_(12)) · d (C_(13)G_(14)C_(15)G_(16)A_(17)A_(18)T_(19)T_(20)C_(21)G_(22)C_(23)G_(24)) , which has one oxidized guanine, 7,8-dihydro-8-oxoguanine (8-oxoG), at the fourth position. The local structural change due to the lesion of 8-oxoG and the global dynamic structure of the 8-oxoG DNA were studied. It was found that the 8-oxoG DNA remained structurally stable during the simulation due to newly produced hydrogen bonds around the (8-oxoG)_4 residue. However, there were distinguishable differences in structural parameters and dynamic property in the 8-oxoG DNA. The conformation around the (8-oxoG)_4 residue departed from the usual conformation of native DNA and took an unique conformation of ε―ζ, in B_(II) conformation and , x in high anti orientation at the (8-oxoG)_4 residue, and adopted a very low helical twist angle at the C_3: G_(22) - (8-oxoG)_4: C_(21) step. Further analysis by principal component analysis indicated that the formation of the hydrogen bonds around the (8-oxoG)_4 residue plays a role as a trigger for the conformational transition of the 8-oxoG DNA in the conformational space.