Energetics of Photoinduced Charge Migration within the Tryptophan Tetrad of an Animal (6–4) Photolyase

Cryptochromes and photolyases are flavoproteins that undergo cascades of electron/hole transfers after excitation of the flavin cofactor. It was recently discovered that animal (6–4) photolyases, as well as animal cryptochromes, feature a chain of four tryptophan residues, while other members of the family contain merely a tryptophan triad. Transient absorption spectroscopy measurements on Xenopus laevis (6–4) photolyase have shown that the fourth residue is effectively involved in photoreduction but at the same time could not unequivocally ascertain the final redox state of this residue. In this article, polarizable molecular dynamics simulations and constrained density functional theory calculations are carried out to reveal the energetics of charge migration along the tryptophan tetrad. Migration toward the fourth tryptophan is found to be thermodynamically favorable. Electron transfer mechanisms are sought either through an incoherent hopping mechanism or through a multiple sites tunneling process. Th...