Thermodynamics of ion binding and occupancy in potassium channels.
Thermodynamics of ion binding and occupancy in potassium channels.
复制标题
钾通道中离子结合和占据的热力学。
DOI：
10.1039/d1sc01887f
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发表时间：
2021-07-01
期刊：
影响因子：
8.4
通讯作者：
Ren P
中科院分区：
文献类型：
--
作者：
Jing Z;Rackers JA;Pratt LR;Liu C;Rempe SB;Ren P
钾离子通道通过有效和选择性地传导钾离子来调节细胞的各种功能。钾离子通道的离子传导机制最近成为一个争论的话题。钾离子通道的晶体结构显示，在选择性过滤器中，四个K+离子与相邻的结合位点结合，而化学直观和分子模拟表明，直接的离子接触是不稳定的。分子动力学（MD）模拟已经在离子通道的传导和门控机制的研究中发挥了重要作用。基于分子动力学模拟，提出了两种假说，其中四离子组态是由于晶体学实验中的平均结构或低温造成的假象。这两个假设已经被不同的实验所支持或挑战。在这里，分子动力学模拟与极化力场验证从头计算被用来研究离子结合热力学。与以前的看法相反，四离子配置被预测为在考虑复杂的静电相互作用和介电屏蔽后是电稳定的。极化在热力学稳定性中起着至关重要的作用。因此，离子传导可能通过简单的单空位和无水机制进行。模拟解释了晶体结构，离子结合实验和最近有争议的诱变实验。这项工作提供了一个清晰的视图的机制，有效的离子传导，并表明在离子通道模拟极化的重要性。极化塑造钾离子通道中离子传导的能量景观。
Potassium channels modulate various cellular functions through efficient and selective conduction of K+ ions. The mechanism of ion conduction in potassium channels has recently emerged as a topic of debate. Crystal structures of potassium channels show four K+ ions bound to adjacent binding sites in the selectivity filter, while chemical intuition and molecular modeling suggest that the direct ion contacts are unstable. Molecular dynamics (MD) simulations have been instrumental in the study of conduction and gating mechanisms of ion channels. Based on MD simulations, two hypotheses have been proposed, in which the four-ion configuration is an artifact due to either averaged structures or low temperature in crystallographic experiments. The two hypotheses have been supported or challenged by different experiments. Here, MD simulations with polarizable force fields validated by ab initio calculations were used to investigate the ion binding thermodynamics. Contrary to previous beliefs, the four-ion configuration was predicted to be thermodynamically stable after accounting for the complex electrostatic interactions and dielectric screening. Polarization plays a critical role in the thermodynamic stabilities. As a result, the ion conduction likely operates through a simple single-vacancy and water-free mechanism. The simulations explained crystal structures, ion binding experiments and recent controversial mutagenesis experiments. This work provides a clear view of the mechanism underlying the efficient ion conduction and demonstrates the importance of polarization in ion channel simulations. Polarization shapes the energy landscape of ion conduction in potassium channels.
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影响因子：
7.7
作者：
Heer, Florian T.;Posson, David J.;Berneche, Simon
通讯作者：
Berneche, Simon
DOI：
10.1039/c6cp02509a
发表时间：
2016-11-09
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
--
作者：
Bell DR;Qi R;Jing Z;Xiang JY;Mejias C;Schnieders MJ;Ponder JW;Ren P
通讯作者：
Ren P
影响因子：
15
作者：
Hamelberg, D;McCammon, JA
通讯作者：
McCammon, JA
DOI：
10.1073/pnas.1805049115
发表时间：
2018-08-07
影响因子：
11.1
作者：
Jing, Zhifeng;Liu, Chengwen;Ren, Pengyu
通讯作者：
Ren, Pengyu
影响因子：
64.8
作者：
通讯作者：
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