用于离子传输的仿生功能纳米通道分子模拟设计

Biological ion channel proteins have many excellent mass-transport properties and remarkable functions. These channel proteins fast transport ions with extremely high permeability and exquisite selectivity, moreover, they can control ion transport with their gates. However, the mechanical properties of these proteins are quite poor, and they often lose bioactivity when leaving the biological setting, which has limited their use in technological applications. Therefore, this project aims to transplant the ion selectivity and gating property of ion channel proteins to carbon nanotubes and graphene nanopores, which have much simpler structures and stronger mechanical properties, by mimicking the key structures and mechanisms of biological ion channels. In this project, based on molecular simulations, inspired by the key structures of sodium channel NavAb, potassium channel KcsA and bacterial channels OprF and OmpA, graphene nanopores and carbon nanotubes are modified with proper functional groups. Molecular dynamics simulations are performed to investigate ion hydration, free energy of ion transport and ionic flux in these designed nanochannels, to assess their ion selectivity and gating property. This project will reveal the relations between the structures of nanochannels and their functions, and shed light on the related mechanisms, which can provide guidance for the development of biomimetic functional nanochannels. Bio-inspired nanochannels designed in this project, which display ion selectivity and /or gating properties, have a wide range of potential applications, such as nanofiltration membranes for ion separation, ion sensors and nanofluidic devices.

生物离子通道蛋白具有优异的传质性能和多种功能，能以非常高的通透性和选择性快速传输离子，且对离子传输门控控制。然而，这些通道蛋白的力学性能较差，非生理环境下容易失活，严重限制其实际应用。因此，本项目拟通过模仿生物离子通道蛋白的关键结构和机制，将其离子选择性和门控功能移植到具有简单结构和良好力学性能的石墨烯纳米孔和碳纳米管。本项目采用分子模拟的方法，受钠离子通道NavAb、钾离子通道KcsA、细菌膜通道蛋白OprF和OmpA的关键结构启发，对石墨烯纳米孔和碳纳米管通道进行仿生修饰；通过纳米通道中离子水化、离子传输自由能和离子流量的模拟研究，对纳米通道的离子选择性或门控功能进行评价，揭示其结构-功能关系，并阐明其功能机制。本项目为仿生功能纳米通道的制备与开发提供指导，设计出选择性传输离子或对离子传输具有门控特性的仿生纳米通道，在用于离子分离的纳滤膜、离子传感器和纳流控装置等领域具有广泛的应用前景。

生物离子通道蛋白具有优异的传质性能和多种功能，能以非常高的通透性和选择性快速传输离子，且对离子传输门控控制。然而，这些通道蛋白的力学性能较差，非生理环境下容易失活，严重限制其实际应用。因此，本项目基于计算机分子模拟，通过模仿生物离子通道蛋白的关键结构和机制，将其离子选择性和门控功能移植到具有简单结构和良好力学性能的石墨烯纳米孔等人工合成纳米通道。首先，研究了外加电场对离子水化的影响，发现只有较强的电场才能干扰离子水化，而且对阴/阳离子水化影响不同。受生物Na+通道NavAb选择性过滤器结构的启发，设计了用4个羧基修饰的仿生石墨烯孔，模拟结果显示，这种石墨烯孔具有离子价键选择性，能选择性结合Ca2+，而选择性传输Na+，离子在孔中的传输都是通过“离子敲击”模式进行。受革兰氏阴性菌的外膜通道蛋白OmpA和OprF的门控机理启发，对合适孔径的石墨烯孔用带正电和带负电的官能团修饰，通过正负静电吸引作用结合在一起，以阻塞孔道，本研究使用带正电的胍基(或氨基)和带负电的羧基；模拟结果表明这种仿生石墨烯孔具有一定的电压门控特性，只有施加足够大外加电场才能打开孔道，而允许离子和水传输。受钾离子通道KcsA的离子选择性过滤器结构的启发，设计了四层用羰基修饰的仿生石墨烯孔，模拟结果显示这种仿生石墨烯孔能选择性传输K+，且K+/Na+选择性比高到10。此外，测试这些仿生石墨烯孔在海水淡化和乙醇/水分离方面的应用。本项目关于仿生功能纳米通道的计算机分子模拟设计，可为仿生功能纳米通道的制备与开发提供指导，这些仿生纳米通道在面向离子分离的纳滤膜、离子传感器和纳流控装置等领域具有广泛的应用前景。