Molecular Dynamics Simulation of 8-Oxoguanine Containing DNA Fragments Reveals Altered Hydration and Ion Binding Patterns

We present results of molecular dynamics (MD) simulations of a double-stranded DNA fragment of sequence 5-d(CGCGAGTTCGCG)-3 and 3-d(GCGCTCAAGCGC)-5 in its native form and altered with guanine in the G6/C19 base pair replaced by 8-oxoguanine (8oxoG). DNA was simulated in solution with Na counterions and explicit water molecules. Trajectories were analyzed for radial distribution functions (RDFs), spatial distribution functions (SDFs), residence times, and occupancies, for both water and ions. Structural parameters of DNA fragments were also considered. Particularly, we report sensible differences in the statistical and dynamical behavior of water and ions between the healthy and lesion containing models. Structural features such as sugar-phosphate backbone torsion angles also significantly differ. We conclude that 8oxoG noticeably modifies its close environment and that the observed changes in the vicinity of the lesion site might help the enzymes in charge of cleansing 8oxoG from human DNA to locate the aberration in its intrahelical context. This work supports the existence of a determinant early recognition mode of 8oxoG for hOGG1. © 2010 American Chemical Society.