Regulating ion transport in peptide nanotubes by tailoring the nanotube lumen chemistry

We use atomistic nonequilibrium molecular dynamics simulations to demonstrate how specific ionic flux in peptide nanotubes can be regulated by tailoring the lumen chemistry through single amino acid substitutions. By varying the size and polarity of the functional group inserted into the nanotube interior, we are able to adjust the Na⁺ flux by over an order of magnitude. Cl^- is consistently denied passage. Bulky, nonpolar groups encourage interactions between the Na⁺ and the peptide backbone carbonyl groups, disrupting the Na⁺ solvation shell and slowing the transport of Na⁺. Small groups have the opposite effect and accelerate flow. These results suggest that relative ion flux and selectivity can be precisely regulated in subnanometer pores by molecularly defining the lumen according to biological principles.