Molecular Simulations of Hydrophobic Gating of Pentameric Ligand Gated Ion Channels: Insights into Water and Ions.
Molecular Simulations of Hydrophobic Gating of Pentameric Ligand Gated Ion Channels: Insights into Water and Ions.
复制标题
五聚体配体门控离子通道疏水门控的分子模拟：对水和离子的见解。
DOI：
10.1021/acs.jpcb.0c09285
复制
发表时间：
2021-02-04
期刊：
影响因子：
--
通讯作者：
Sansom MSP
中科院分区：
文献类型：
--
作者：
Rao S;Klesse G;Lynch CI;Tucker SJ;Sansom MSP
离子通道是在生物膜上形成门控纳米孔的蛋白质。许多通道表现出疏水门控，从而通过局部去湿来实现孔的功能性闭合。五聚体配体门控离子通道(PLGICs)为疏水门控提供了一个重要的生物学例子。分子模拟研究比较了添加剂和极化模型，表明疏水门控的预测与所采用的模型是稳健的。然而，极化模型表明疏水孔衬区域与氯离子具有良好的相互作用，这与合成载体和通道蛋白都有关。封闭的pLGIC疏水栅电润湿需要太高的电压，生理上不能发生，但可能会为可切换纳米孔的设计提供依据。对∼200通道的全局分析为基于结构的(关闭的)疏水门预测提供了一个简单的启发式方法。基于模拟的分析为解释新航道结构的功能状态提供了帮助。这些研究表明了解水和离子在离子通道呈现的纳米受限环境中的行为的重要性。
Ion channels are proteins which form gated nanopores in biological membranes. Many channels exhibit hydrophobic gating, whereby functional closure of a pore occurs by local dewetting. The pentameric ligand gated ion channels (pLGICs) provide a biologically important example of hydrophobic gating. Molecular simulation studies comparing additive vs polarizable models indicate predictions of hydrophobic gating are robust to the model employed. However, polarizable models suggest favorable interactions of hydrophobic pore-lining regions with chloride ions, of relevance to both synthetic carriers and channel proteins. Electrowetting of a closed pLGIC hydrophobic gate requires too high a voltage to occur physiologically but may inform designs for switchable nanopores. Global analysis of ∼200 channels yields a simple heuristic for structure-based prediction of (closed) hydrophobic gates. Simulation-based analysis is shown to provide an aid to interpretation of functional states of new channel structures. These studies indicate the importance of understanding the behavior of water and ions within the nanoconfined environment presented by ion channels.
登录
查看更多内容
影响因子：
16.6
作者：
Aryal, Prafulla;Abd-Wahab, Firdaus;Bucci, Giovanna;Sansom, Mark S. P.;Tucker, Stephen J.
通讯作者：
Tucker, Stephen J.
影响因子：
2
作者：
Beckstein, O;Sansom, MSP
通讯作者：
Sansom, MSP
影响因子：
8.6
作者：
Allen, R;Melchionna, S;Hansen, JP
通讯作者：
Hansen, JP
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：
Corry, B
通讯作者：
Corry, B