Cryptochromes are signaling proteins activated by photoexcitation of the flavin adenine dinucleotide (FAD) cofactor. Although extensive research has been performed, the mechanism for this allosteric process is still unknown. We constructed three computational models, corresponding to different redox states of the FAD cofactor in Drosophila cryptochrome (dCRY). Analyses of the dynamics trajectories reveal that the activation process occurs in the semiquinone state FAD^−●, resulting from excited-state electron transfer. The Arg³⁸¹-Asp⁴¹⁰ salt bridge acts as an allosteric switch, regulated by the change in the redox state of FAD. In turn, Asp⁴¹⁰ forms new hydrogen bonds, connecting allosteric networks of the amino-terminal and carboxyl-terminal domains initially separated in the resting state. The expansion to a global dynamic network leads to enhanced protein fluctuations, an increase in the radius of gyration, and the expulsion of the carboxyl-terminal tail. These structural features are in accord with mutations and spectroscopic experiments.

隐花色素是由黄素腺嘌呤二核苷酸 (FAD) 辅因子的光激发激活的信号蛋白。尽管已经进行了广泛的研究，但这种变构过程的机制仍然未知。我们构建了三个计算模型，对应于果蝇隐花色素 (dCRY) 中 FAD 辅因子的不同氧化还原状态。动力学轨迹分析表明，激活过程发生在半醌态FAD ^-●，由激发态电子转移引起。Arg ³⁸¹ -Asp ⁴¹⁰盐桥充当变构开关，受 FAD 氧化还原状态变化的调节。反过来，Asp ⁴¹⁰形成新的氢键，连接最初在静止状态下分离的氨基末端和羧基末端结构域的变构网络。向全局动态网络的扩展导致蛋白质波动增强、回转半径增加以及羧基末端尾部的排出。这些结构特征与突变和光谱实验一致。