From foldamers to functional pores: a force field for oligourea-based desalination channels

Abstract

Sea water desalination is a critical solution to global water scarcity, primarily relying on membrane-based technologies and reverse osmosis. Artificial water channels (AWCs) offer a promising solution for next-generation desalination membranes. Very promising channel building blocks for AWC is oligourea foldamers repeats. These biomimetic molecules, composed of unnatural amino acids, self-assemble into protein-like superhelical channels with water-filled pores, making them ideal candidates for selective water transport. In silico studies provide essential support to experimental efforts in designing novel oligoureas. However, such studies require a dedicated force field for now unavailable for these molecules. In this work, we developed a tailored force field for oligoureas by adapting parameters from two established protein force field families: CHARMM (CHARMM36m) and Amber (GAFF2), using their structural similarities to natural amino acids. Our objective was to identify a force field that reliably preserves the structural integrity of oligourea foldamers. We evaluated two distinct oligoureas using molecular dynamics (MD) simulations across increasing system sizes. By comparing simulation results with experimental data, we assessed key structural features, including folding patterns, stability, and pore shapes. Our findings demonstrate that the CHARMM-based force field consistently reproduces experimental observations for both foldamers, outperforming the Amber-based alternative. This newly developed CHARMM-based force field paves the way for further exploration of oligoureas, enabling deeper insights into their stability and efficiency in sea water desalination.