Water, Solute, and\nIon Transport in De Novo-Designed\nMembrane Protein Channels

Biological organisms engineer peptide sequences to fold\ninto membrane\npore proteins capable of performing a wide variety of transport functions.\nSynthetic de novo-designed membrane pores can mimic this approach\nto achieve a potentially even larger set of functions. Here we explore\nwater, solute, and ion transport in three de novo designed β-barrel\nmembrane channels in the 5–10 Å pore size range. We show\nthat these proteins form passive membrane pores with high water transport\nefficiencies and size rejection characteristics consistent with the\npore size encoded in the protein structure. Ion conductance and ion\nselectivity measurements also show trends consistent with the pore\nsize, with the two larger pores showing weak cation selectivity. MD\nsimulations of water and ion transport and solute size exclusion are\nconsistent with the experimental trends and provide further insights\ninto structure–function correlations in these membrane pores.