Ion permeation in the NanC porin from Escherichia coli: free energy calculations along pathways identified by coarse-grain simulations.
Ion permeation in the NanC porin from Escherichia coli: free energy calculations along pathways identified by coarse-grain simulations.
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大肠杆菌 NanC 孔蛋白中的离子渗透：沿着粗粒模拟确定的路径进行自由能计算
DOI：
10.1021/jp4081838
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
P. Carloni
中科院分区：
文献类型：
--
作者：
Dreyer J;P. Strodel;E. Ippoliti;J. Finnerty;R. Eisenberg;P. Carloni
利用最近发现的细菌蛋白质N-乙酰神经氨酸诱导通道（NanC）的X射线结构，我们计算研究了K+和Cl-离子的渗透。我们确定的离子渗透途径，很可能是人口使用粗粒蒙特卡罗模拟。接下来，我们使用这些途径作为反应坐标伞采样为基础的自由能模拟。我们发现不同的tubelike途径连接特定的结合位点K+，更明显的是，Cl-离子。这两种离子渗透孔蛋白保留几乎所有的第一水化壳。计算得到Cl ~-和K ~+的自由能垒分别为G #~（-4）kJ/mol和G #~（-8）kJ/mol。在与这些值相关的近似值，在这项工作中详细讨论，我们建议，孔蛋白是轻微的选择性Cl-与K+。我们的建议是一致的实验观察到的弱Cl-超过K+的选择性。后者的理由建议通过与以前的计算强阴离子选择性孔蛋白的比较。
Using the X-ray structure of a recently discovered bacterial protein, theN-acetylneuraminic acid-inducible channel (NanC), we investigate computationally K+and Cl–ions’ permeation. We identify ion permeation pathways that are likely to be populated using coarse-grain Monte Carlo simulations. Next, we use these pathways as reaction coordinates for umbrella sampling-based free energy simulations. We find distinct tubelike pathways connecting specific binding sites for K+and, more pronounced, for Cl–ions. Both ions permeate the porin preserving almost all of their first hydration shell. The calculated free energy barriers areG#≈ 4 kJ/mol andG#≈ 8 kJ/mol for Cl–and K+, respectively. Within the approximations associated with these values, discussed in detail in this work, we suggest that the porin is slightly selective for Cl–versus K+. Our suggestion is consistent with the experimentally observed weak Cl–over K+selectivity. A rationale for the latter is suggested by a comparison with previous calculations on strongly anion selective porins.