Bacteriophytochromes are light-sensing biological machines that interconvert between two spectroscopically distinct states, Pr and Pfr. The relative stability of the two states is opposite in canonical and bathy bacteriophytochromes but in both cases the switch between them is triggered by a photoisomerization of an embedded bilin chromophore, the effects of which propagate throughout the protein with different timescales. Here, we applied an integrated multiscale strategy of (QM/)MM molecular dynamics simulations and excited-state QM/MM nonadiabatic dynamics with enhanced sampling techniques to the Agrobacterium fabrum bathy phytochrome and compared the results with those obtained for the canonical phytochrome Deinococcus radiodurans. Contrary to what recently suggested, we found that the photoactivation of both phytochromes is directly triggered by the same photoisomerization process involving an hula-twist motion. However, only in the bathy phytochrome the photoproduct evolves into a heterogeneous and dynamic intermediate, Lumi-F, in which the bilin has reached the final (Pr) configurational state. Moreover, the protein pocket of the bathy phytochrome responds in a microsecond timescale, by reorienting several aminoacidic residues and causing the spine to tilt.

中文翻译：

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通过多尺度建模揭示深海和典型细菌光敏色素光活化机制的相似性和差异

细菌光敏色素是光感应生物机器，可在两种光谱上不同的状态（Pr 和 Pfr）之间相互转换。这两种状态的相对稳定性在经典和深海细菌光敏色素中是相反的，但在这两种情况下，它们之间的转换都是由嵌入的胆碱生色团的光异构化触发的，其效应以不同的时间尺度在整个蛋白质中传播。在这里，我们将 (QM/)MM 分子动力学模拟和激发态 QM/MM 非绝热动力学的集成多尺度策略与增强采样技术应用于农杆菌深水光敏色素，并将结果与​​典型的耐辐射球菌光敏色素获得的结果进行比较。与最近提出的相反，我们发现两种光敏色素的光活化是由涉及呼拉扭转运动的相同光异构化过程直接触发的。然而，只有在深海光敏色素中，光产物才会演变成异质且动态的中间体 Lumi-F，其中 bilin 已达到最终 (Pr) 构型状态。此外，深海光敏色素的蛋白质口袋在微秒的时间尺度内做出反应，通过重新定位几个氨基酸残基并导致脊柱倾斜。