Blue light using flavin (BLUF) photoreceptor proteins are critical for many light-activated biological processes and are promising candidates for optogenetics because of their modular nature and long-range signaling capabilities. Although the photocycle of the Slr1694 BLUF domain has been characterized experimentally, the identity of the light-adapted state following photoexcitation of the bound flavin remains elusive. Herein hybrid quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations of this photocycle provide a nonequilibrium dynamical picture of a possible mechanism for the formation of the light-adapted state. Photoexcitation of the flavin induces a forward proton-coupled electron transfer (PCET) process that leads to the formation of an imidic acid tautomer of Gln50. The calculations herein show that the subsequent rotation of Gln50 allows a reverse PCET process that retains this tautomeric form. In the resulting purported light-adapted state, the glutamine tautomer forms a hydrogen bond with the flavin carbonyl group. Additional ensemble-averaged QM/MM calculations of the dark-adapted and purported light-adapted states demonstrate that the light-adapted state with the imidic acid glutamine tautomer reproduces the experimentally observed spectroscopic signatures. Specifically, the calculations reproduce the red shifts in the flavin electronic absorption and carbonyl stretch infrared spectra in the light-adapted state. Further hydrogen-bonding analyses suggest the formation of hydrogen-bonding interactions between the flavin and Arg65 in the light-adapted state, providing a plausible explanation for the experimental observation of faster photoinduced PCET in this state. These characteristics of the light-adapted state may also be essential for the long-range signaling capabilities of this photoreceptor protein.

使用黄素（BLUF）感光蛋白的蓝光对于许多光激活的生物过程至关重要，由于它们的模块性质和远距离信号传递能力，它们有望成为光遗传学的候选物。尽管已经通过实验表征了Srr1694 BLUF结构域的光循环，但是光激发结合的黄素后的光适应性状态仍然难以捉摸。本文中，该光循环的混合量子力学/分子力学（QM / MM）分子动力学模拟提供了形成光适应态的可能机理的非平衡动力学图。黄素的光激发诱导正向质子偶联电子转移（PCET）过程，导致形成Gln50的亚氨酸互变异构体。本文的计算表明，Gln50的后续旋转允许保留该互变异构形式的反向PCET过程。在所得的声称的光适应性状态下，谷氨酰胺互变异构体与黄素羰基形成氢键。暗适应和据称轻适应状态的整体平均QM / MM计算表明，具有亚胺二酸谷氨酰胺互变异构体的轻适应状态可再现实验观察到的光谱特征。具体而言，该计算再现了在光适应状态下黄素电子吸收和羰基拉伸红外光谱的红移。进一步的氢键分析表明，在光适应状态下，黄素和Arg65之间形成了氢键相互作用，为这种状态下更快的光诱导PCET的实验观察提供了合理的解释。光适应状态的这些特征对于该感光蛋白的远程信号传递能力也可能是必不可少的。