Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Computational Biology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
J Mol Biol. 2021 Aug 20;433(17):167002. doi: 10.1016/j.jmb.2021.167002. Epub 2021 Apr 20.
Potassium channels play critical roles in many physiological processes, providing a selective permeation route for K ions in and out of a cell, by employing a carefully designed selectivity filter, evolutionarily conserved from viruses to mammals. The structure of the selectivity filter was determined at atomic resolution by x-ray crystallography, showing a tight coordination of desolvated K ions by the channel. However, the molecular mechanism of K ions permeation through potassium channels remains unclear, with structural, functional and computational studies often providing conflicting data and interpretations. In this review, we will present the proposed mechanisms, discuss their origins, and will critically assess them against all available data. General properties shared by all potassium channels are introduced first, followed by the introduction of two main mechanisms of ion permeation: soft and direct knock-on. Then, we will discuss critical computational and experimental studies that shaped the field. We will especially focus on molecular dynamics (MD) simulations, that provided mechanistic and energetic aspects of K permeation, but at the same time created long-standing controversies. Further challenges and possible solutions are presented as well.
钾通道在许多生理过程中发挥着关键作用，通过使用精心设计的选择性过滤器，为细胞内外的 K 离子提供了选择性渗透途径，该选择性过滤器在从病毒到哺乳动物的进化过程中得到了保守。通过 X 射线晶体学，在原子分辨率下确定了选择性过滤器的结构，显示出通道对去溶剂化 K 离子的紧密配位。然而，K 离子通过钾通道的渗透的分子机制仍不清楚，结构、功能和计算研究经常提供相互矛盾的数据和解释。在这篇综述中，我们将提出建议的机制，讨论它们的起源，并根据所有可用数据对它们进行批判性评估。首先介绍所有钾通道共有的一般特性，然后介绍离子渗透的两种主要机制：软和直接撞击。然后，我们将讨论塑造该领域的关键计算和实验研究。我们将特别关注提供 K 渗透的机制和能量方面的分子动力学 (MD) 模拟，但同时也引发了长期存在的争议。还提出了进一步的挑战和可能的解决方案。
