Investigating the Electron Transfer Cascade in Cryptochrome 4 of Different Birds

Cryptochrome 4 (Cry4) has emerged over recent decades as a prominent candidate for mediating magnetoreception in birds. Upon photoexcitation of its flavin adenine dinucleotide (FAD) cofactor, Cry4 can initiate an electron transfer (ET) cascade through a conserved chain of four tryptophan residues. This process leads to the formation of a charge-seprated radical pair, [FAD·− TrpH·+], whose lifetime is modulated by external magnetic fields. Recent experimental efforts have focused on elucidating the ET dynamics of European robin Cry4 (ErCry4) and comparing its magnetic sensitivity to that of other avian orthologs, such as pigeon's Cry4 (ClCry4). In this work, we employed the Marcus theory of electron transfer in conjunction with polarisable embedding QM/MM calculations to compute ET rates along the FAD–tryptophan chain in ErCry4. Our results yield time-resolved population dynamics that show good agreement with available transient absorption data. We then extended the same computational analysis to ClCry4, for which experimental ET rates have not yet been reported. This comparative study reveals a substantial similarity in the radical pair lifetimes between the two species and provides mechanistic insights into the structural factors influencing their ET behaviour.