A QM/MM study on the fast photocycle of blue light using flavin photoreceptors in their light-adapted/active form.

Based on QM/MM calculations using a combination of time-dependent Hartree-Fock and coupled cluster response theory a mechanism is proposed for the photocycle of blue light using flavin (BLUF) domains in the signaling/light adapted conformation. In analogy to the dark-adapted form, a charge transfer state drives proton transfer from the highly conserved tyrosine residue to the flavin chromophore. The latter step is mediated by the adjacent glutamine residue, which, in the light adapted conformation, exists as its imidic tautomer. However, before the proton transfer is even halfway completed, a conical intersection seam between the charge transfer and ground state is reached. Two channels for the decay back to the initial light-adapted conformation are open, a rapid one leading directly through the funnel of the conical intersection, bypassing the formation of the biradical intermediate, and a slower one via the biradical intermediate. The mechanism as proposed here: (i) explains the very rapid photocycle; and (ii) confirms the concept of photoirreversibility, both of which have been experimentally observed for BLUF domains in their light-adapted conformations.