Model for proton transport coupled to protein conformational change: application to proton pumping in the bacteriorhodopsin photocycle.
Model for proton transport coupled to protein conformational change: application to proton pumping in the bacteriorhodopsin photocycle.
复制标题
质子传输与蛋白质构象变化耦合的模型：在细菌视紫红质光循环中质子泵的应用。
DOI：
10.1021/ja060742d
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发表时间：
2006
影响因子：
15
通讯作者：
Bashford,Donald
中科院分区：
文献类型：
--
作者：
Ferreira,AntonioM;Bashford,Donald
蛋白质系统中，质子运输耦合到构象变化，如在质子泵和马达驱动的质子动力的建模方法。先前开发的方法用于计算PKa值在蛋白质中使用的宏观介电模型扩展超出平衡的情况下，通过电离微观状态和一组离散的构象定义的状态的系统的时间演化的主方程模型。宏观介电模型提供质子化微观状态变化的自由能变化，而获得构象变化和弛豫速率的能量学的方法，主方程所需的其他成分，是系统相关的。该方法适用于光活化的质子泵，细菌视紫红质，从实验中使用构象自由能的差异，并通过三个可调参数治疗弛豫速率。该模型被发现泵质子的效率相对不敏感的参数选择在很宽的参数值范围内，和已知的光周期的主要功能，从很早的M到返回到静止状态的再现。这些参数范围的边界使得短程质子转移比长程质子转移快，长程质子转移又比构象变化快。弛豫速率不依赖于构象。结果表明，一个“可及性开关”，虽然不排除，是不需要的，矢量质子运输可以通过耦合的电离和构象状态的能量。
A modeling method is presented for protein systems in which proton transport is coupled to conformational change, as in proton pumps and in motors driven by the proton-motive force. Previously developed methods for calculating pKavalues in proteins using a macroscopic dielectric model are extended beyond the equilibrium case to a master-equation model for the time evolution of the system through states defined by ionization microstate and a discrete set of conformers. The macroscopic dielectric model supplies free energy changes for changes of protonation microstate, while the method for obtaining the energetics of conformational change and the relaxation rates, the other ingredients needed for the master equation, are system dependent. The method is applied to the photoactivated proton pump, bacteriorhodopsin, using conformational free energy differences from experiment and treating relaxation rates through three adjustable parameters. The model is found to pump protons with an efficiency relatively insensitive to parameter choice over a wide range of parameter values, and most of the main features of the known photocycle from very early M to the return to the resting state are reproduced. The boundaries of these parameter ranges are such that short-range proton transfers are faster than longer-range ones, which in turn are faster than conformational changes. No relaxation rates depend on conformation. The results suggest that an “accessibility switch”, while not ruled out, is not required and that vectorial proton transport can be achieved through the coupling of the energetics of ionization and conformational states.