Benzophenone and DNA: Evidence for a Double Insertion Mode and Its Spectral Signature

From explicit solvent molecular dynamics simulations, we probe the existence of two stable and competitive interaction modes between an alternating poly(dA-dT) decamer and benzophenone, a minor groove adduct and a double insertion structure in which the central base pair is ejected, with hydrogen bonding with proximal groups, locking the DNA–drug complex. The extensive analysis of noncovalent interactions provides a rationale for the existence of this mode, never reported yet between DNA and any organic photosensitizer. We evidence a highly characteristic signature in our simulated circular dichroism spectra that may provide useful guidance for the future experimental efforts, as well as for theoretical investigations aiming at elucidating the energy-transfer mechanism between benzophenone and thymines.