Salvadori Giacomo, Mennucci Benedetta
Institute for Computational Biomedicine (INM-9/IAS-5), Forschungszentrum Jülich, 52428 Jülich, Germany.
Dipartimento di Chimica e Chimica Industriale, University of Pisa, 56124 Pisa, Italy.
J Phys Chem Lett. 2024 Aug 8;15(31):8078-8084. doi: 10.1021/acs.jpclett.4c01823. Epub 2024 Aug 1.
Bacteriophytochromes are light-sensing biological machines that switch between two photoreversible states, Pr and Pfr. Their relative stability is opposite in canonical and bathy bacteriophytochromes, but in both cases the switch between them is triggered by the photoisomerization of an embedded bilin chromophore. We applied an integrated multiscale strategy of excited-state QM/MM nonadiabatic dynamics and (QM/)MM molecular dynamics simulations with enhanced sampling techniques to the bathy phytochrome and compared the results with those obtained for the canonical phytochrome . Contrary to what recently suggested, we found that photoactivation in both phytochromes is triggered by the same hula-twist motion of the bilin chromophore. However, only in the bathy phytochrome, the bilin reaches the final rotated structure already in the first intermediate. This allows a reorientation of the binding pocket in a microsecond time scale, which can propagate through the entire protein causing the spine to tilt.
细菌光敏色素是一种光感应生物机器，可在两种光可逆状态Pr和Pfr之间切换。它们的相对稳定性在典型细菌光敏色素和深海细菌光敏色素中相反，但在这两种情况下，它们之间的切换都是由嵌入的胆色素发色团的光异构化触发的。我们将激发态量子力学/分子力学非绝热动力学和（量子力学/）分子力学分子动力学模拟的综合多尺度策略与增强采样技术应用于深海光敏色素，并将结果与典型光敏色素的结果进行了比较。与最近的建议相反，我们发现两种光敏色素中的光激活都是由胆色素发色团相同的呼啦圈扭转运动触发的。然而，只有在深海光敏色素中，胆色素在第一个中间体中就已经达到了最终的旋转结构。这允许结合口袋在微秒时间尺度上重新定向，这可以传播到整个蛋白质，导致脊柱倾斜。
