Our previous NMR studies have shown that DNA containing an alpha anomeric residue is kinked and has an enlarged minor groove at the site of the lesion. Both of these features facilitate the interaction with the enzyme. Biochemical studies have shown that the substrate quality of the damaged DNA for endonuclease IV is greatly influenced by the base pairs surrounding the lesion. The flanking sequences in turn are expected to affect both the kink and minor groove topologies, thereby modulating the “repairability” of a given DNA lesion. In this study we are examining the structural and temporal effects of different flanking sequences on 30 ns molecular dynamics simulations (Amber) utilizing different restraints, solvent conditions, and force fields.