Electrostatic origin of the mechanochemical rotary mechanism and the catalytic dwell of F1-ATPase
Electrostatic origin of the mechanochemical rotary mechanism and the catalytic dwell of F1-ATPase
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DOI：
10.1073/pnas.1117024108
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发表时间：
2011-12-20
影响因子：
11.1
通讯作者：
Warshel, Arieh
中科院分区：
文献类型：
--
作者：
Mukherjee, Shayantani;Warshel, Arieh
理解生命过程中能量转导的本质需要对ATP酶将ATP转化为ADP的能量学进行定量描述。以前的尝试，这样做提供了一个有趣的见解，但不能占旋转机制的非唯象的结构/能量描述。特别地，在没有关于模拟过程中的这些状态的任何先验信息的情况下，解释80度和40度旋转子状态的观测是非常具有挑战性的。在这里，我们使用一个粗粒度的模型F1-ATP酶和生成，没有调整的现象学参数，一个基于结构的自由能景观，再现的机械化学过程的能量。结果表明，旋转路径上的景观沿着是由静电自由能决定的，而不是由空间位阻效应决定的。此外，所产生的表面和相应的朗之万动力学模拟确定了一个隐藏的构象障碍，提供了一个新的基本解释的催化驻留和照明的能量转换过程的性质。
Understanding the nature of energy transduction in life processes requires a quantitative description of the energetics of the conversion of ATP to ADP by ATPases. Previous attempts to do so have provided an interesting insight but could not account for the rotary mechanism by a nonphenomenological structure/energy description. In particular it has been very challenging to account for the observations of the 80 degrees and 40 degrees rotational substates, without any prior information about such states in the simulation procedure. Here we use a coarse-grained model of F1-ATPase and generate, without the adjustment of phenomenological parameters, a structure-based free energy landscape that reproduces the energetics of the mechanochemical process. It is found that the landscape along the relevant rotary path is determined by the electrostatic free energy and not by steric effects. Furthermore, the generated surface and the corresponding Langevin dynamics simulations identify a hidden conformational barrier that provides a new fundamental interpretation of the catalytic dwell and illuminate the nature of the energy conversion process.