Decrypting the Non-Adiabatic 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 events via a tryptophan chain, eventually generating a radical pair crucial for signaling. Despite extensive studies, the initial photoinduced electron transfer (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 non-adiabatic pathways and protein environment on the reaction kinetics and quantum efficiency of the ET. To address this gap, we performed extensive non-adiabatic and adiabatic dynamics simulations with on-the-fly multireference ab initio electronic structure calculations of Arabidopsis thaliana cryptochrome 1 (AtCRY1). Our results reveal a novel mechanism in which rapid non-radiative decay from higher-lying singlet states leads to charge separation, complementing the slower adiabatic ET on the S1 state hindered by a newly identified low-energy S1 local excitation minimum. Furthermore, the protein environment stabilizes tryptophan orientations, facilitating subsequent electron transfer steps. These insights significantly enhance our understanding of photoinduced ET in cryptochromes and the structure-function relationships in photoreceptors.