Probing the interactions of the solvated electron with DNA by molecular dynamics simulations: bromodeoxyuridine substituted DNA

Solvated electrons () are produced during water radiolysis and can interact with biological substrates, including DNA. To augment DNA damage, radiosensitizers such as bromo-deoxyuridine (BUdR), often referred to as an “electron affinic radiosensitizer”, are incorporated in place of isosteric thymidine. However, little is known about the primary interactions of with DNA. In the present study we addressed this problem by applying molecular modeling and molecular dynamics (MD) simulations to a system of normal (BUdR·A)-DNA and a hydrated electron, where the excess electron was modeled as a localized (H₂O)₆ anionic cluster. Our goals were to evaluate the suitability of the MD simulations for this application; to characterize the motion of around DNA (e.g., diffusion coefficients); to identify and describe configurational states of close localization to DNA; and to evaluate the structural dynamics of DNA in the presence of . The results indicate that has distinct space-preferences for forming close contacts with DNA and is more likely to interact directly with nucleotides other than BUdR. Several classes of DNA - contact sites, all within the major groove, were distinguished depending on the structure of the intermediate water layer H-bonding pattern (or its absence, i.e., a direct H-bonding of with DNA bases). Large-scale structural perturbations were identified during and after the approached the DNA from the major groove side, coupled with deeper penetration of sodium counterions in the minor groove. Figure A rare configuration showing direct interaction between the solvated electron and DNA, where (yellow) and N7(A16) are H-bonded. The close approach from the major groove side invokes deep Na⁺ (magenta) penetration into the minor DNA groove (Fig. 7a).