ORIGINAL PAPER Probing the interactions of the solvated electron with DNA by molecular dynamics simulations: bromodeoxyuridine substituted DNA Tsvetan G. Gantchev & Darel J. Hunting Received: 13 November 2007 / Accepted: 28 February 2008 / Published online: 15 April 2008 # Springer-Verlag 2008 Abstract Solvated electrons (e À aq ) 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 e À aq 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 e À (H 2 O) 6 anionic cluster. Our goals were to evaluate the suitability of the MD simulations for this application; to characterize the motion of e À aq around DNA (e.g., diffusion coefficients); to identify and describe configurational states of close e À aq localization to DNA; and to evaluate the structural dynamics of DNA in the presence of e À aq . The results indicate that e À aq 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 - e À aq 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 e À aq with DNA bases). Large-scale structural perturbations were identified during and after the e À aq approached the DNA from the major groove side, coupled with deeper penetration of sodium counterions in the minor groove. Keywords Bromodeoxyuridine (BUdR) . DNA conformation . Electron attachment . Hydrated electron . Molecular dynamics . Molecular modeling . Radiosensitization Introduction Hydrated electrons, e À aq are a major species produced during water radiolysis with a radiation yield as high as that of ·OH radicals (G=2.8×10 -7 mol J -1 )[1]. During the last decade, the intriguing structural and optical properties of e À aq [2], and more generally the solution chemistry of excess electrons in molecular liquids have received growing attention by theoreticians [3–8] and spectroscopists [9– 12]. Studies of anionic water clusters presuppose solvated electron structural models of various hierarchy, e À (H 2 O) n , n=6–50 and many have been tested to different extents experimentally. Regardless of the alternative e À aq models, e. g., (OH - …H 3 O) aq type complexes [13], the e À + 6H 2 O (Kevan’ s, one shell [14, 15]), and the e À + (6+12)H 2 O (two shells), the concept of localized or cavity anions has been well supported by spectroscopic and theoretical calculations and remains the most popular. Hydrated electrons can efficiently interact with nucleo- bases and isolated nucleotides, with bimolecular rate constants in the range of (0.9–1.7)×10 10 M -1 s -1 [1]. In purified DNA, the decrease of reaction efficiency is about two orders of magnitude compared with isolated nucleo- tides [1]. The exact reasons behind this decline are not known, but it is safe to assume that the macromolecular structure at all levels (primary, secondary and tertiary) together with the DNA and Debay-Hückel layer dynamics play a role in the modulation of reactivity. During the last several years, studies on excess electron transfer in DNA J Mol Model (2008) 14:451–464 DOI 10.1007/s00894-008-0296-x T. G. Gantchev (*) : D. J. Hunting Department of Nuclear Medicine & Radiobiology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada e-mail: tsvetan.gantchev@usherbrooke.ca