Decrypting the Non-Adiabatic Photoinduced Electron Transfer Mechanism in Light-Sensing Cryptochrome

Cryptochromes are blue light photoreceptors found in organisms from plants to animals, playing various critical roles in life processes such as 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 photoinduced electron transfer mechanism involving non-radiative decay from higher-lying singlet states, which proceeds much faster than the adiabatic electron transfer on the S1 state. The adiabatic process is hindered by a newly discovered low-energy S1 local excitation minimum. In contrast, non-adiabatic relaxation can rapidly reach a dynamically stable S1 charge-transfer minimum, setting the stage for subsequent electron transfer steps. Additionally, the protein environment stabilizes the orientation of tryptophan residues, facilitating later ET events between them while hindering the initial FAD-W400 transfer. These new insights greatly enhance our fundamental understanding of photoinduced electron transfer in cryptochromes and the structure-function relationships in photoreceptors in general.