Clarendon Laboratory, Department of Physics, University of Oxford, Oxford, UK; Department of Biochemistry, University of Oxford, Oxford, UK.
Department of Biochemistry, University of Oxford, Oxford, UK.
Biophys J. 2022 Jun 7;121(11):2014-2026. doi: 10.1016/j.bpj.2022.05.006. Epub 2022 May 7.
Interactions between ions and water at hydrophobic interfaces within ion channels and nanopores are suggested to play a key role in the movement of ions across biological membranes. Previous molecular-dynamics simulations have shown that anion affinity for aqueous/hydrophobic interfaces can be markedly influenced by including polarization effects through an electronic continuum correction. Here, we designed a model biomimetic nanopore to imitate the polar pore openings and hydrophobic gating regions found in pentameric ligand-gated ion channels. Molecular-dynamics simulations were then performed using both a non-polarizable force field and the electronic-continuum-correction method to investigate the behavior of water, Na, and Cl ions confined within the hydrophobic region of the nanopore. Number-density distributions revealed preferential Cl adsorption to the hydrophobic pore walls, with this interfacial layer largely devoid of Na. Free-energy profiles for Na and Cl permeating the pore also display an energy-barrier reduction associated with the localization of Cl to this hydrophobic interface, and the hydration-number profiles reflect a corresponding reduction in the first hydration shell of Cl. Crucially, these ion effects were only observed through inclusion of effective polarization, which therefore suggests that polarizability may be essential for an accurate description for the behavior of ions and water within hydrophobic nanoscale pores, especially those that conduct Cl.
离子与水在离子通道和纳米孔内疏水区界面的相互作用被认为在离子跨生物膜的运动中起着关键作用。以前的分子动力学模拟表明，通过包括电子连续体修正的极化效应，可以显著影响阴离子对水/疏水区界面的亲和力。在这里，我们设计了一个模型仿生纳米孔，以模拟五聚体配体门控离子通道中发现的极性孔开口和疏水区门控区域。然后使用非极化力场和电子连续体修正方法进行分子动力学模拟，研究水、Na 和 Cl 离子在纳米孔疏水区中的行为。数密度分布显示 Cl 优先吸附到疏水区的孔壁上，该界面层中几乎没有 Na。Na 和 Cl 渗透孔的自由能曲线也显示出与 Cl 定位到该疏水区界面相关的能垒降低，水合数曲线反映了 Cl 的第一水合壳相应减少。至关重要的是，只有通过包括有效的极化，才能观察到这些离子效应，因此表明极化率对于准确描述疏水分子纳米孔内离子和水的行为可能是必不可少的，特别是那些传导 Cl 的纳米孔。
