Molecular Design Of Biomimetic Functional Nanochannels

Biological protein channels have many remarkable properties and fascinating functions,such as fast mass-transport with high permeability and selectivity, high water permeabilitywith salt-rejection, ion-selectivity, gating, ionic current-rectification and environmentalresponsiveness. Using molecular dynamics (MD) simulations, this study aims to transplantthese properties and functions to biomimetic nanochannels by mimicking the key structuresand mechanisms of biological channel proteins, which might lead to a wide range of potentialapplications, such as in chemical separation, nanomedicines, reverse osmosis desalinationmembranes and novel nanofluidic systems for accurate chemical analysis. The successfuldesign of biomimetic nanochannels may help elucidate the essential ingredients for thefunctions of biological channels. This study could discover new phenomenon arising inelectrolyte solutions confined in nanochannels. Additionally, the suitability of amino acids forcarbon nanotube (CNT) aqueous dispersions is assessed in this study.Steered MD and umbrella sampling simulations are performed to study the process ofNa+, K+and Cl traversing through (6,6),(7,7),(8,8),(9,9) and (10,10) CNTs and ionhydration in CNTs is analyzed. The results show that ions are hindered from entering narrowCNTs at the entrance; however, it is easy for ions to leave narrow CNTs into bulk solution atthe exit. There is almost no hindrance for ions to translocate through wide CNTs. The freeenergy barriers for ions translocating through CNTs decrease sharply with the increase ofdiameter. Different free energy barriers of Na+, K+and Cl entering CNTs indicate that CNTshave an inherent ion selectivity. When ions traverse through CNTs, coordination numbers andpreferential orientation of water molecules in coordination shells of ions are different fromthose in bulk, which determine the dehydration energies of ions and affect free energy barriersof ions traversing CNTs and the ion selectivity of CNTs. It is found that the interaction of Na+and K+with the water molecules is enhanced in CNT(8,8), but is similar or weaker than inbulk in the other CNTs. In bulk, water molecules orient in specific directions around ions dueto the electrostatic interaction between them. Under the confinement of CNTs, the hydrogenbonds formed in the first hydration shell of Na+and K+disturb this orientation greatly. Anexception is in CNT(8,8), where the dipole orientation is even more favorable for cations thanin bulk due to the formation of a unique ice-like water structure that aligns the watermolecules in specific directions. In contrast, the coordination number is more important thanhydration shell orientation in determining the Cl--water interaction. Additionally, thepreference for ions to adopt specific radial positions in the CNTs also affects ionic hydration. Inspired by the key structures of biological ion channel proteins, we have performed MDsimulations to design biomimetic graphene nanopores that can discriminate between Na+andK+, two ions with very similar properties. The simulation results show that undertransmembrane voltage bias, a nanopore containing four carbonyl groups to mimic theselectivity filter of the KcsA K+channel, preferentially conducts K+over Na+. A nanoporefunctionalized by four negatively charged carboxylate groups to mimic the selectivity filter ofthe NavAb Na+channel, selectively binds Na+but transports K+over Na+. Interestingly, theion selectivity of the smaller diameter pore containing three carboxylate groups can be tunedby changing the magnitude of the applied voltage bias. Under lower voltage bias, it transportsions in a single file manner and exhibits Na+selectivity, dictated by the knock-on ionconduction and selective blockage by Na+. Under higher voltage bias, the nanopore is K+selective, as the blockage by Na+is destabilized and the stronger affinity for carboxylategroups slows the passage of Na+compared with K+.Gates in many biological channels are formed by a constriction ringed with hydrophobicresidues which can prevent ion conduction even when they are not completely physicallyoccluded. We use MD simulations to design a nanogate inspired by this hydrophobic gatingmechanism. Deforming a CNT(12,12) with an external force can form a hydrophobicconstriction in the tube centre that controls ion conduction. The simulation results show thatincreasing the magnitude of the applied force narrows the constriction and lowers the fluxesof K+and Cl-found under an electric field. With the exerted force lager than5nN, theconstriction blocks the conduction of K+and Cl-due to partial dehydration while allowing fora noticeable water flux. Ion conduction can revert back to the unperturbed level upon theforce retraction, suggesting the reversibility of the nanogate. The force can be exerted byavailable experimental facilities, such as atomic force microscope (AFM) tips. It is found thatpartial dehydration in a continuous water-filled hydrophobic constriction is enough to closethe channel, while full dewetting is not necessarily required.The adsorption of20standard amino acids on CNT(6,6) at a concentration of0.17M andpH7.0has been studied by MD simulations. Simulation results show that among the20amino acids, phenylalanine, tyrosine, tryptophan and arginine exhibit the strongest affinity forCNT(6,6). They adsorb to the tube and form very stable aggregates. Phenylalanine, tyrosineand tryptophan interact with the tube via the strong stacking of their aromatic rings.Interestingly, the strong attraction of arginine to CNT(6,6) mainly attributes to itsguanidinium group, which strongly interacts with the tube and forms multiple salt bridges.The negatively charged carboxylate and positively charged ammonium groups of these adsorbed amino acids extend away from the tube surface and point towards aqueous solution,which facilitates the solubilization of CNTs in water, and may be able to provide electrostaticrepulsion forces to prevent CNT agglomeration. The results of this work provide a theoreticalsupport for using amino acids as novel CNT dispersing agents and help to understandCNT-protein interactions.