The protonation state of the Glu-71/Asp-80 residues in the KcsA potassium channel: A first-principles QM/MM molecular dynamics study
The protonation state of the Glu-71/Asp-80 residues in the KcsA potassium channel: A first-principles QM/MM molecular dynamics study
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DOI：
10.1529/biophysj.106.102509
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发表时间：
2007-10-01
影响因子：
3.4
通讯作者：
Rothlisberger, Ursula
中科院分区：
文献类型：
--
作者：
Bucher, Denis;Guidoni, Leonardo;Rothlisberger, Ursula
尽管KCSAK1通道的一些X射线结构已经晶化，但有关离子渗透机制和选择性的质子化状态的几个问题。过滤器的可电离侧链仍然是开放的。利用第一性原理量子力学/分子力学模拟方法，研究了位于选择性滤光片附近的两个重要残基Glu-71和Asp-80的质子化状态。动力学结果表明，两个残基之间共享一个质子，并略有偏爱Glu-71。发现质子在皮秒时间尺度上交换，这是一个在经典分子动力学中观察不到的有趣现象。对滤光片不同离子负载状态的模拟表明，质子转移的概率与滤光片的占有率有关。此外，Glu-71/Asp-80对能够调节势能Pro。K1离子沿孔轴平移时所经历的LE。这些理论预测和最近的实验结果表明，过滤器结构的变化可能与Glu-Asp质子化状态的变化有关，这反过来会影响离子的转移。
Although a few x-ray structures of the KcsA K 1 channel have been crystallized several issues concerning the mechanisms of the ionic permeation and the protonation state of the selectivity. filter ionizable side chains are still open. Using a first- principles quantum mechanical/molecular mechanical simulation approach, we have investigated the protonation state of Glu-71 and Asp-80, two important residues located in the vicinity of the selectivity filter. Results from the dynamics show that a proton is shared between the two residues, with a slight preference for Glu-71. The proton is found to exchange on the picosecond timescale, an interesting phenomenon that cannot be observed in classical molecular dynamics. Simulations of different ionic loading states of the filter show that the probability for the proton transfer is correlated with the filter occupancy. In addition, the Glu-71/Asp- 80 pair is able to modulate the potential energy pro. le experienced by a K 1 ion as it translates along the pore axis. These theoretical predictions, along with recent experimental results, suggest that changes of the filter structure could be associated with a shift in the Glu-Asp protonation state, which in turn would influence the ion translocation.