Salt-Excluding Artificial Water Channels Exhibiting Enhanced Dipolar Water and Proton Translocation

Aquaporins (AQPs) are biological water channels known for fast water transport (∼108–109 molecules/s/channel) with ion exclusion. Few synthetic channels have been designed to mimic this high water permeability, and none reject ions at a significant level. Selective water translocation has previously been shown to depend on water-wires spanning the AQP pore that reverse their orientation, combined with correlated channel motions. No quantitative correlation between the dipolar orientation of the water-wires and their effects on water and proton translocation has been reported. Here, we use complementary X-ray structural data, bilayer transport experiments, and molecular dynamics (MD) simulations to gain key insights and quantify transport. We report artificial imidazole-quartet water channels with 2.6 Å pores, similar to AQP channels, that encapsulate oriented dipolar water-wires in a confined chiral conduit. These channels are able to transport ∼106 water molecules/s, which is within 2 orders of magnitude of AQPs’ rates, and reject all ions except protons. The proton conductance is high (∼5 H+/s/channel) and approximately half that of the M2 proton channel at neutral pH. Chirality is a key feature influencing channel efficiency.

水通道蛋白（Aquaporins, AQPs）是一类以快速水转运（约10^8~10^9个分子/秒/通道）和离子排阻特性著称的生物水通道。迄今仅有少量人工合成通道被设计用于模拟这种高水通透性，且无一能实现高效离子排阻。既往研究表明，选择性水转运依赖于跨水通道蛋白孔道的水链——这类水链可发生取向反转，并与通道的协同运动相结合。目前尚无关于水链偶极取向与其对水和质子转运的影响之间定量关联的报道。本研究结合互补性X射线结构数据、双层膜转运实验与分子动力学（molecular dynamics, MD）模拟，获取了关键研究见解并实现了转运过程的定量分析。我们构建了孔径为2.6埃的人工咪唑四聚体水通道，其结构与水通道蛋白通道相似，可在受限手性通道内封装取向性偶极水链。该类通道每秒可转运约10^6个水分子，与水通道蛋白的转运速率相差不超过两个数量级，且可排阻除质子外的所有离子。其质子电导可达约5个质子/秒/通道，在中性pH条件下约为M2质子通道（M2 proton channel）的一半。手性是影响该通道转运效率的核心特征。