Flavin Charge Transfer Transitions Assist DNA Photolyase Electron Transfer

This contribution describes molecular dynamics, semi‐empirical and ab‐initio studies of the primary photo‐induced electron transfer reaction in DNA photolyase. DNA photolyases are $FADH−$‐containing proteins that repair UV‐damaged DNA by photo‐induced electron transfer. A DNA photolyase recognizes and binds to cyclobutatne pyrimidine dimer lesions of DNA. The protein repairs a bound lesion by transferring an electron to the lesion from $FADH−,$ upon photo‐excitation of $FADH−$ with 350–450 nm light. We compute the lowest singlet excited states of $FADH−$ in DNA photolyase using INDO/S configuration interaction, time‐dependent density‐functional, and time‐dependent Hartree‐Fock methods. The calculations identify the lowest singlet excited state of $FADH−$ that is populated after photo‐excitation and that acts as the electron donor. For this donor state we compute conformationally‐averaged tunneling matrix elements to empty electron‐acceptor states of a thymine dimer bound to photolyase. The conformational averaging involves different $FADH−$‐thymine dimer confromations obtained from molecular dynamics simulations of the solvated protein with a thymine dimer docked in its active site. The tunneling matrix element computations use INDO/S‐level Green's function, energy splitting, and Generalized Mulliken‐Hush methods. These calculations indicate that photo‐excitation of $FADH−$ causes a $π→π*$ charge‐transfer transition that shifts electron density to the side of the flavin isoalloxazine ring that is adjacent to the docked thymine dimer. This shift in electron density enhances the $FADH−$‐to‐dimer electronic coupling, thus inducing rapid electron transfer.