Artificial water channels
Monodispersed angstrom-size pores embedded in a suitable matrix are promising for highly selective membrane-based separations. They can provide substantial energy savings in water treatment and small molecule bioseparations. Such pores present as membrane proteins (chiefly aquaporin-based) are commonplace in biological membranes but difficult to implement in synthetic industrial membranes and have modest selectivity without tunable selectivity. Here we present PoreDesigner, a design workflow to redesign the robust beta-barrel Outer Membrane Protein F as a scaffold to access three specific pore designs that exclude solutes larger than sucrose (>360 Da), glucose (>180 Da), and salt (>58 Da) respectively. PoreDesigner also enables us to design any specified pore size (spanning 3–10 Å), engineer its pore profile, and chemistry. These redesigned pores may be ideal for conducting sub-nm aqueous separations with permeabilities exceeding those of classical biological water channels, aquaporins, by more than an order of magnitude at over 10 billion water molecules per channel per second.
Aquaporin (AQP) proteins function as highly efficient water transport channels that support homeostasis in many types of living cells. Their structure-function relationships have been characterized extensively in fundamental and applied research, primarily via structural analysis, mutational studies, and computational approaches. The present study evaluates the effects of progressive truncations on the permeability and ionic conductivity of AQP-1 (bovine). The use of truncations to determine critical features has not been considered previously, as physical truncation of AQP is likely not technically feasible due to the ornate arrangement of six interwoven alpha helices in a single pore structure. However, structures not obtainable through protein assembly can be realized via synthetic chemistry approaches and studied using molecular dynamics (MD) simulations. Here, we apply the MD method to characterize the permeability of AQP variants truncated along the pore axis from both cytoplasmic and extracellular sides of the channel. The simulation results suggest that AQP-1 can retain its function even after deletion of up to 50% of the channel’s length, representing 50% of proteins’s molecular mass. Deletions such as these are expected to greatly simplify future biomimicry efforts of reproducing the AQP functionality using synthetic macromolecules. This study demonstrates the potential of in silico approaches to support the creation of streamlined functional analogs of biological molecular machines.
Artificial nanoscale water channels are the future of cheap, low-power water filtration and desalinization. Biological water channels such as the aquaporin membrane protein selectively pass water across the cell membranes of living creatures, yet they are difficult to use in technological applications. Over the past decade a number of artificial channels such as carbon nanotubes have been designed to imitate the function of aquaporins. A new single-molecule water channel called pillararene, or PAP, bears the potential to outshine all artificial water channels known to date with its high permeability, ease of precision manufacture, and ready assembly into high-throughput membranes. A PAP channel has a single benzyl ring at its center (shown in blue in the image) and ten peptide-like arms (purple) that extend from the ring accross the membrane (green). Water (red and white) passes single file through the carbon nanotube-like ring of the channel while the peptide arms anchor the channel into a lipid bilayer.