Nonadiabatic Photodynamics of Retinal Protonated Schiff Base in Channelrhodopsin 2
Nonadiabatic Photodynamics of Retinal Protonated Schiff Base in Channelrhodopsin 2
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视紫红质通道 2 中视网膜质子化希夫碱的非绝热光动力学
DOI：
10.1021/acs.jpclett.9b00701
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Martínez, Todd J.
中科院分区：
文献类型：
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作者：
Liang, Ruibin;Liu, Fang;Martínez, Todd J.
通道视紫红质2(ChR2)是一种光门离子通道，是光遗传学研究的重要工具。视网膜质子化Schiff碱(RPSB)在ChR2中的光异构化触发通道激活。尽管ChR2在光遗传学中很重要，但光异构化和通道激活的详细机制仍不完全清楚。在这里，我们报告了用计算机模拟来研究光异构化机理及其对ChR2活化的影响。用从头算多重产卵(AIMS)方法和量子力学/分子力学(QM/MM)方法对ChR2进行了非绝热动力学模拟，QM区采用有限系综Kohn-Sham(REKS)方法。我们的结果与光谱测量结果很好地一致，并揭示了RPSB异构化是围绕C13=C14键的高度专一性的，遵循“失败的自行车-踏板”机制。此外，RPSB的光异构化促进了其去质子化，并部分增加了通道中的水合水平，这可能触发随后的通道开放和离子传导。
Channelrhodopsin 2 (ChR2) is a light-gated ion channel and an important tool in optogenetics. Photoisomerization of retinal protonated Schiff base (RPSB) in ChR2 triggers channel activation. Despite the importance of ChR2 in optogenetics, the detailed mechanism for photoisomerization and channel activation is still not fully understood. Here, we report on computer simulations to investigate the photoisomerization mechanism and its effect on the activation of ChR2. Nonadiabatic dynamics simulation of ChR2 was carried out using the ab initio multiple spawning (AIMS) method and quantum mechanics/molecular mechanics (QM/MM) with a restricted ensemble Kohn–Sham (REKS) treatment of the QM region. Our results agree well with spectroscopic measurements and reveal that the RPSB isomerization is highly specific around the C13=C14bond and follows the “aborted bicycle-pedal” mechanism. In addition, RPSB photoisomerization facilitates its deprotonation and partially increases the hydration level in the channel, which could trigger subsequent channel opening and ion conduction.