Department of Biochemistry, University of Oxford , South Parks Road, Oxford OX1 3QU, Oxford, United Kingdom.
ACS Nano. 2014 Nov 25;8(11):11268-79. doi: 10.1021/nn503930p. Epub 2014 Oct 20.
Nanopores in membranes have a range of potential applications. Biomimetic design of nanopores aims to mimic key functions of biological pores within a stable template structure. Molecular dynamics simulations have been used to test whether a simple β-barrel protein nanopore can be modified to incorporate a hydrophobic barrier to permeation. Simulations have been used to evaluate functional properties of such nanopores, using water flux as a proxy for ionic conductance. The behavior of these model pores has been characterized as a function of pore size and of the hydrophobicity of the amino acid side chains lining the narrow central constriction of the pore. Potential of mean force calculations have been used to calculate free energy landscapes for water and for ion permeation in selected models. These studies demonstrate that a hydrophobic barrier can indeed be designed into a β-barrel protein nanopore, and that the height of the barrier can be adjusted by modifying the number of consecutive rings of hydrophobic side chains. A hydrophobic barrier prevents both water and ion permeation even though the pore is sterically unoccluded. These results both provide insights into the nature of hydrophobic gating in biological pores and channels, and furthermore demonstrate that simple design features may be computationally transplanted into β-barrel membrane proteins to generate functionally complex nanopores.
膜中的纳米孔具有广泛的潜在应用。纳米孔的仿生设计旨在模拟生物孔在稳定模板结构内的关键功能。分子动力学模拟已被用于测试简单的β-桶状蛋白纳米孔是否可以被修改为包含阻止渗透的疏水性屏障。模拟已被用于评估此类纳米孔的功能特性，使用水通量作为离子电导率的替代物。这些模型孔的行为已被表征为孔径和孔内狭窄中央收缩处排列的疏水性氨基酸侧链的疏水性的函数。平均力势能计算已被用于计算选定模型中水和离子渗透的自由能景观。这些研究表明，疏水性屏障确实可以设计到β-桶状蛋白纳米孔中，并且可以通过修改疏水性侧链的连续环数来调整屏障的高度。疏水性屏障可防止水和离子渗透，即使孔在空间上没有被阻塞。这些结果不仅提供了对生物孔和通道中疏水性门控本质的深入了解，而且还证明了简单的设计特征可以通过计算移植到β-桶状膜蛋白中，以产生功能复杂的纳米孔。
