在Channelrhodopsin 2中对光异构的静电控制
Ruibin Liang1,2, Jimmy K Yu1,2,3, Jan Meisner1,2
1Department of Chemistry and The PULSE Institute, Stanford University, Stanford, California 94305, United States.
Journal of the American Chemical Society
|April 1, 2021
概括
尽管光周期更快,但E123T Channelrhodopsin 2 (ChR2) 突变因静电变化而呈现较慢的光异构. 这项研究阐明了CHR2
科学领域:
- 视觉遗传学
- 生物物理
- 计算化学
背景情况:
- 道素2 (ChR2) 是神经元刺激的关键光遗传工具.
- ChR2的E123T突变呈现出更快的光循环,但最初的光异构化速度较慢.
- E123T突变改变了视网膜质子 Schiff 基 (RPSB) 周围的局部电场.
研究的目的:
- 阐明 ChR2 E123T 突变体中的 RPSB 光异构化机制.
- 了解静电环境的变化如何影响CHR2的光化学反应.
- 为设计改进的光遗传工具提供见解.
主要方法:
- 一开始的非动力学模拟.
- 激发状态的自由能量计算.
- 反应路径搜索.
主要成果:
- 模拟证实了对E123T ChR2的红移光谱和较慢光异构的实验发现.
- 对 WT 和 E123T ChR2 的类似光异构化量子产量进行预测.
- 突变诱导的电荷中和增加异构化障碍,修改反应路径,并改变光状态的稳定性.
结论:
- E123T突变显著影响了ChR2中的RPSB光异构化机制.
- 静电相互作用在控制 ChR2 的光化学性质方面起着至关重要的作用.
- 这些发现有助于对微生物素光化学和光遗传工具设计的分子理解.
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