Simulation of ion transport through an N-acetylneuraminic acid-inducible membrane channel: from understanding to engineering.
Simulation of ion transport through an N-acetylneuraminic acid-inducible membrane channel: from understanding to engineering.
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通过 N-乙酰神经氨酸诱导膜通道模拟离子传输：从理解到工程
DOI：
10.1021/jp408495v
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
U. Kleinekathöfer
中科院分区：
文献类型：
--
作者：
N. Modi;U. Kleinekathöfer
N-乙酰神经氨酸诱导通道（NanC）是大肠杆菌的外膜通道。该孔蛋白折叠成 12 链 β-桶，形成管状。电生理学实验揭示了相对于所施加电压的方向的不对称电导和通道的弱阴离子选择性。为此，我们进行了全原子分子动力学 (MD) 模拟，以破译 NanC 通道的离子传输特性。浓度相关的应用场 MD 模拟恢复了通道的不对称电导特性和阴离子选择性，与实验一致。进一步的分子分析揭示了通道内不对称电荷分布作为电导不对称基础的作用。此外，内通道壁上带电残基的特殊分布导致 Cl- 离子比 K+ 离子更快的渗透，从而导致 NanC 的阴离子选择性。这些发现得到了位置相关的扩散系数和从无偏 MD 模拟得出的平均力分布的潜力的充分支持。更进一步，我们能够通过导致增强的不对称电导和阴离子选择性的突变来在计算机中设计 NanC 通道。例如，E186Q 突变体将 NanC 转变为良好的分子二极管，在相反的偏置电压下离子电流比约为 3:1。
N-acetylneuraminic acid-inducible channel (NanC) is an outer membrane channel of Escherichia coli. This porin folds as a 12-stranded β-barrel leading to a tubular shape. Electrophysiological experiments have revealed an asymmetric conductance with respect to the direction of the applied voltage and a weak anion selectivity of the channel. To this end, we performed all-atom molecular dynamics (MD) simulations to decipher the ion transport properties of the NanC channel. Concentration-dependent applied-field MD simulations recover the asymmetric conductance property and the anion selectivity of the channel in agreement with experiments. Further molecular analysis revealed the role of the asymmetric charge distribution inside the channel as the basis of the asymmetry in conductance. In addition, the particular distribution of charged residues at the inner channel walls leads to a faster permeation of Cl–ions compared to K+ions resulting in the anion selectivity of NanC. These findings are well supported by position-dependent diffusion coefficients and potential of mean force profiles derived from unbiased MD simulations. Taking one step further, we were able to engineer the NanC channel in silico by mutations leading to enhanced asymmetric conductances and anion selectivities. The E186Q mutant, for example, changes NanC into a decent molecular diode with an ionic current ratio of about 3:1 for opposite bias voltages.
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影响因子：
3.4
作者：
Noskov, SY;Im, W;Roux, B
通讯作者：
Roux, B
影响因子：
2.9
作者：
Niraj Modi;Iván Bárcena-Uribarri;M. Bains;R. Benz;R. Hancock;U. Kleinekathöfer
通讯作者：
Niraj Modi;Iván Bárcena-Uribarri;M. Bains;R. Benz;R. Hancock;U. Kleinekathöfer
影响因子：
3.4
作者：
Aksimentiev, A;Schulten, K
通讯作者：
Schulten, K
影响因子：
3.4
作者：
Gumbart, James;Khalili-Araghi, Fatemeh;Sotomayor, Marcos;Roux, Benoit
通讯作者：
Roux, Benoit
DOI：
10.1021/jz301637d
发表时间：
2012-11
期刊：
The journal of physical chemistry letters
影响因子：
--
作者：
Niraj Modi;R. Benz;R. Hancock;U. Kleinekathöfer
通讯作者：
Niraj Modi;R. Benz;R. Hancock;U. Kleinekathöfer