Molecular dynamics simulation of 8-oxoguanine lesioned DNA complexed with repair enzyme hOGG1

Pinak, M.

The molecular dynamics (MD) simulations of DNA mutagenic oxidative lesion 8-oxoG, single and complexed with the repair enzyme hOGG1, were performed. In the case of simulation of single DNA molecule the broken hydrogen bonds resulting in locally collapsed B-DNA structure were observed at the lesion site. In addition the adenine on the complementary strand was flipped-out of the DNA double helix. In the case of simulation of DNA and repair enzyme hOGG1, the DNA-enzyme complex was formed after 500 picoseconds of MD that lasted stable until the simulation was terminated at 1 ns. The N-terminus of arginine 313 was located close to the phosphodiester bond of nucleotide with 8-oxoG enabling chemical reactions between amino acid and lesion. Phosphodiester bond at C5'of 8-oxoG was at the position close to the N-terminus of arginine 313. The water mediated hydrogen bonds network was formed in each contact area between DNA and enzyme further enhancing the stability of complex.