Department of Theoretical Chemical Biology, Institute of Physical Chemistry, Karlsruhe Institute of Technology, Kaiserstrasse 12, 76131 Karlsruhe, Germany.
Phys Chem Chem Phys. 2018 Nov 7;20(43):27501-27509. doi: 10.1039/c8cp05210g.
The first event of the channelrhodopsin-2 (ChR2) photocycle, i.e. trans-to-cis photoisomerization, is studied by means of quantum mechanics/molecular mechanics, taking into account the flexible retinal environment in the ground state. By treating the chromophore at the ab initio multiconfigurational level of theory, we can rationalize the experimental findings based on pump-probe spectroscopy, explaining the different and more complex scenario found for ChR2 in comparison to other rhodopsins. In particular, we find that depending on the hydrogen bonding pattern, different excited states are involved, hence making it possible to suggest one pattern as the most productive. Moreover, after photoisomerization the structure of the first photocycle intermediate, P5001, is characterized by simulating the infrared spectrum and compared to available experimental data. This was obtained by extensive molecular dynamics, where the chromophore is described by a semi-empirical method based on density functional theory. The results clearly identify which counterion is responsible for accepting the proton from the retinal Schiff base: the side chain of the glutamic acid E123.
通道视紫红质-2（ChR2）光循环的第一个事件，即反式-顺式光异构化，通过考虑基态中灵活的视网膜环境，通过量子力学/分子力学进行研究。通过在从头算多组态理论水平上处理发色团，我们可以根据泵浦-探测光谱学的实验结果进行合理化解释，这解释了 ChR2 与其他视蛋白相比，其不同且更复杂的情况。具体来说，我们发现，根据氢键模式的不同，涉及不同的激发态，因此可以提出一种模式作为最有效的模式。此外，在光异构化之后，通过模拟红外光谱并与现有实验数据进行比较，来描述第一个光循环中间体 P5001 的结构。这是通过广泛的分子动力学获得的，其中发色团由基于密度泛函理论的半经验方法描述。结果清楚地确定了哪个抗衡离子负责从视网膜席夫碱中接受质子：谷氨酸 E123 的侧链。
