Applications of metal–organic frameworks (MOFs) functionalized with biomolecules have primarily focused on the use of these frameworks for bioimaging, catalysis, chiral separation, nanomotors, and drug delivery. However, their use in the design of artificial water channels (AWCs) has yet to be explored. In this work, we computationally explore the performance of a zwitterionic alanine-functionalized Ni-CPO-27 MOF as an AWC. Using density functional theory (DFT) calculations and equilibrium/nonequilibrium molecular dynamics (MD) simulations, the stability, water permeability, and ion selectivity of the proposed AWC are studied. The DFT calculations predict that zwitterionic alanine binds to the coordinatively unsaturated Ni sites almost twofold stronger compared to water. Using the quantum theory of atoms in molecules, it is also found that the zwitterionic alanine molecules are further stabilized through hydrogen bonding between their carboxylate (COO–) and amino (NH3+) groups. Nonequilibrium MD simulations show that the proposed AWC possesses a high osmotic water permeability of 2.2 ± 0.3 × 10–15 cm3/s/channel, which lies between that observed in aquaporin-0 and aquaporin-1 proteins, while completely excluding Na+ and Cl– ions from the channel. The free energies associated with the water and ion transport show that fast water transport may be attributed to the relatively low free energy barriers for water in the channel, whereas the ion exclusion is due to large free energy barriers that the ions cannot overcome even under 100 MPa of applied pressure. By using a crystalline material, the proposed design of an amino acid-functionalized MOF-based AWC represents a departure from previously developed AWCs, which rely on the self-assembly of curated molecules in lipid bilayers or polymer matrices and are susceptible to long-term stability issues
