Department of Chemistry, James Franck Institute, Institute for Biophysical Dynamics, and Computation Institute, University of Chicago, Chicago, Illinois, USA.
Biophys J. 2011 Nov 16;101(10):L47-9. doi: 10.1016/j.bpj.2011.10.021. Epub 2011 Nov 15.
Using a reactive molecular dynamics simulation methodology, the free energy barrier for water-mediated proton transport between the two proton gating residues Glu(203) and Glu(148) in the ClC-ec1 antiporter, including the Grotthuss mechanism of proton hopping, was calculated. Three different chloride-binding states, with 1), both the central and internal Cl(-), 2), the central Cl(-) only, and 3), the internal Cl(-) only, were considered and the coupling to the H(+) transport studied. The results show that both the central and internal Cl(-) are essential for the proton transport from Glu(203) to Glu(148) to have a favorite free energy driving force. The rotation of the Glu(148) side chain was also found to be independent of the internal chloride binding state. These results emphasize the importance of the 2:1 stoichiometry of this well-studied Cl(-)/H(+) antiporter.
采用反应分子动力学模拟方法，计算了 ClC-ec1 反向转运蛋白中两个质子门控残基 Glu(203)和 Glu(148)之间通过水介导的质子传递的自由能势垒，包括质子跳跃的 Grotthuss 机制。考虑了三种不同的氯离子结合态，分别为 1）中央和内部 Cl(-)，2）仅中央 Cl(-)，以及 3）仅内部 Cl(-)，并研究了与 H(+)传输的耦合。结果表明，中央和内部 Cl(-)对于质子从 Glu(203)传递到 Glu(148)具有有利的自由能驱动力都是必不可少的。还发现 Glu(148)侧链的旋转与内部氯离子结合状态无关。这些结果强调了这个研究充分的 Cl(-)/H(+)反向转运蛋白 2:1 化学计量的重要性。
