A COMPUTATIONAL ATOMISTIC MODEL OF RADIATION DAMAGE TO DNA By BULENT AYDOGAN A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY

ions at the nucleobases. The percent •OH attack probabilities to the various sugar hydrogens are shown in Figure 3.11 for model calculations in which sugar only or sugar plus base reactions are considered. In both cases, the total numbers of sugar attacks are normalized to 100%. Also plotted in Figure 3.11 are %SASA values (Rprobe = 1.2 Å and normalized only to the sugar hydrogens) and the experimental data on site-specific cleavage rates by Balasubramanian et al. Several conclusions may be drawn from the data of Figure 3.11. First, the inclusion of base reactions does not greatly influence the %•OH sugar attacks at C(4') and at C(3'); however, inclusion of the base reactions increases the percentage of attacks at C(5') with a corresponding drop in attacks at C(2') and C(1') hydrogen atoms. Due to their proximity to the nucleobases, the latter carbon sites in the sugar moiety must compete for approaching hydroxyl with interaction sites in the nucleobases (see Table 3.2 for a comparison of reaction radii). It has been shown that the hydroxyl reactions at C(5’) and C(4’) lead to unique chemical products that can be experimentally detected [Balasubramanian et al. 1998; Cadet et al. 1999; Scholes 1983; Scholes and Simic 1968; von Sonntag 1987]. These chemical products are 5’-aldehyde and 3’-phosphoglycolate for hydroxyl abstraction reactions at the C(5’) and C(4’), respectively [Balasubramanian et al. 1998; von Sonntag 1987]. Several initial hydrogen abstraction reactions can, in principle, lead to production of 3’-phosphate [Balasubramanian et al. 1998]. There is, however, little information as to