Decrypting the Nonadiabatic Photoinduced Electron Transfer Mechanism in Light-Sensing Cryptochrome.

Cryptochromes are blue light photoreceptors in organisms from plants to animals that are essential for circadian rhythms, phototropism, and magnetoreception. In light-sensing cryptochromes, the photoexcitation of the flavin adenine dinucleotide (FAD) cofactor triggers a cascade of electron transfer (ET) events via a tryptophan chain, eventually generating a radical pair crucial for signaling. Despite extensive studies, the initial photoinduced ET from a neighboring tryptophan residue to FAD remains unclear due to the complexity of simulating all-atom dynamics in excited states, particularly regarding the roles of nonadiabatic pathways and protein environment on the reaction kinetics and quantum efficiency of the ET. To address this gap, we performed extensive nonadiabatic and adiabatic dynamics simulations with on-the-fly multireference electronic structure calculations of cryptochrome 1 (CRY1). Our results reveal a novel mechanism in which rapid nonradiative decay from higher-lying singlet states leads to charge separation, complementing the slower adiabatic ET on the S state hindered by a newly identified low-energy S local excitation minimum. Furthermore, the protein environment stabilizes tryptophan orientations, facilitating subsequent ET steps. These insights significantly enhance our understanding of photoinduced ET in cryptochromes and the structure-function relationships in photoreceptors.