title: Molecular dynamics simulation of 7, 8-dihydro-8-oxoguanine DNA.
abstract: 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(1)G(2)C(3)(8-oxoG)(4)A(5)A(6)T(7)T(8)C(9)G(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 epsilon-zeta in B(II) conformation and chi 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):C21) 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.
authors.affiliation: Center for Promotion of Computational Science and Engineering, Japan Atomic Energy Research Institute, 2-2-54 Nakameguro, Meguro-ku, Tokyo, 153-0061, Japan. isida@koma.jaeri.go.jp
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ishida
mesh_terms: D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry; D025341:Principal Component Analysis; D011487:Protein Conformation; D055672:Static Electricity; D014867:Water / Q000737:chemistry
chemical_list: C453560:7,8-dihydro-8-oxoguanine; D014867:Water; D006147:Guanine; D004247:DNA; D010100:Oxygen