Physics Colloquium - Friday, Oct. 20th, 2006, 4:00 P.M.
E300 Math/Science Center; Refreshments at 3:30 P.M. in Room E200
We use quantum mechanics/molecular mechanics (QM/MM) calculations to address the oxidative DNA damage process resulting from water addition to guanine (G) radical cations. In particular, we consider DNA duplexes containing GG steps embedded in AGGA or TGGT sequences (A,T for adenine and thymine, respectively) and we focus on the direction- and sequence-sensitivity of the oxidation process at the GG doublets. In accord with gel electrophoresis and auto-radiography experiments, our calculations show that the oxidation process occurs predominantly at the 5'-G of GG doublets, and that it is markedly sequence-sensitive. Our study suggests that the rate of water addition at guanine radical cations is governed mainly by steric effects.