Molecular dynamics simulation of proton-transfer coupled rotations in ATP synthase FO motor
Molecular dynamics simulation of proton-transfer coupled rotations in ATP synthase FO motor
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DOI：
10.1038/s41598-020-65004-1
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发表时间：
2020-05-19
影响因子：
4.6
通讯作者：
Takada, Shoji
中科院分区：
文献类型：
--
作者：
Kubo, Shintaroh;Niina, Toru;Takada, Shoji
FOF 1 ATP合成酶中的F-O马达在质子动力的驱动下旋转其转子。虽然早期的研究阐明了其中的基本机制，但高分辨率冷冻电子显微镜的最新进展使其能够在结构细节上研究质子转移耦合的F-O旋转动力学。本文采用Monte Carlo/分子动力学混合模拟方法，研究了酵母线粒体F-O的可逆动力学。我们得到了在ATP合成模式下每一个质子转移的F-O的36度步进旋转和在ATP水解模式下的质子泵。在这两种模式下，最突出的路径交替采样状态与两个和三个去质子化的谷氨酸在c-环，其中的c-环旋转一步。在最佳条件下，F-O型电动机的自由能转换效率可达90%左右。此外，关键谷氨酸和高度保守的精氨酸的突变增加了质子泄漏，并显着降低了耦合，与以前的实验相一致。本研究为进一步研究ATP合成酶等提供了一个简单的化学反应耦合分子动力学模拟框架。
The F-O motor in FOF1 ATP synthase rotates its rotor driven by the proton motive force. While earlier studies elucidated basic mechanisms therein, recent advances in high-resolution cryo-electron microscopy enabled to investigate proton-transfer coupled F-O rotary dynamics at structural details. Here, taking a hybrid Monte Carlo/molecular dynamics simulation method, we studied reversible dynamics of a yeast mitochondrial F-O. We obtained the 36 degrees-stepwise rotations of F-O per one proton transfer in the ATP synthesis mode and the proton pumping in the ATP hydrolysis mode. In both modes, the most prominent path alternatively sampled states with two and three deprotonated glutamates in c-ring, by which the c-ring rotates one step. The free energy transduction efficiency in the model F-O motor reached similar to 90% in optimal conditions. Moreover, mutations in key glutamate and a highly conserved arginine increased proton leakage and markedly decreased the coupling, in harmony with previous experiments. This study provides a simple framework of simulations for chemical-reaction coupled molecular dynamics calling for further studies in ATP synthase and others.