Multiscale Simulation of Photoinduced Electron Transfer in Cryptochrome 4 from European Robin and Pigeon Indicates a...

Cryptochrome 4 (Cry4) is a leading candidate for mediating magnetoreception in birds. Upon photoexcitation of its flavin adenine dinucleotide (FAD) cofactor, Cry4 initiates an electron transfer (ET) cascade through a conserved chain of four tryptophan residues, resulting in a spin-correlated radical pair whose lifetime is sensitive to external magnetic fields. Recent studies have focused on characterizing the ET dynamics in European robin Cry4 (ErCry4) and assessing its magnetosensitivity relative to other avian orthologs, such as pigeon Cry4 (ClCry4). In this work, we employed a multiscale computational approach combining AlphaFold structural modeling, Molecular Dynamics simulations, and polarizable embedding QM/MM calculations to compute ET rates along the FAD-tryptophan chain in ErCry4 and ClCry4. Our results show good agreement with available transient absorption spectroscopy data. We find a high degree of similarity in the radical pair lifetimes between the two species and provide a structural explanation for this behavior.