Parameterization and atomistic simulations of biomimetic membranes.

Biomimetic membranes, designed by combining proteins or protein-mimics with self-assembled block copolymers, are emerging as novel hybrid materials with applications in the next generation of sensing and separation devices. However, designing such membranes requires a fundamental understanding of the atomic-scale interactions between biological channel proteins and their non-native polymeric membrane environment as it affects their stability and function. In principle, all-atom molecular dynamics (MD) simulations are well-suited to probe the atomistic details of channel/membrane interactions, but the absence of interatomic potentials is a major limiting factor in conducting such simulations. To alleviate this, we have developed CHARMM force-field compatible parameters and conducted all-atom explicit-solvent MD simulations of biomimetic membranes composed of block copolymers of poly(butadiene), poly(isoprene), and poly(ethylene oxide). Consistent with scaling laws and literature data, we report measurements on several structural properties that inform on molecular-scale features of chain conformations. Finally, we report simulations of a synthetic transport channel in selected membranes and characterize its functional behavior by measuring the single-channel water permeability. We suggest that the interatomic potentials and membrane models reported here could be useful in studies of other proteins as well as for deriving potentials for coarse-grained models to permit future simulations of large-scale protein/polymer membranes.

Water Dynamics in a Peptide-appended Pillar[5]arene Artificial Channel in Lipid and Biomimetic Membranes.

Peptide-appended Pillar[5]arene (PAP) is an artificial water channel that can be incorporated into lipid and polymeric membranes to achieve high permeability and enhanced selectivity for angstrom-scale separations [Shen et al. Nat. Commun. 9:2294 (2018)]. In comparison to commonly studied rigid carbon nanotubes, PAP channels are conformationally flexible, yet these channels allow a high water permeability [Y. Liu and H. Vashisth Phys. Chem. Chem. Phys. 21:22711 (2019)]. Using molecular dynamics (MD) simulations, we study water dynamics in PAP channels embedded in biological (lipid) and biomimetic (block-copolymer) membranes to probe the effect of the membrane environment on water transport characteristics of PAP channels. We have resolved the free energy surface and local minima for water diffusion within the channel in each type of membrane. We find that water follows single file transport with low free-energy barriers in regions surroundings the central ring of the PAP channel and the single file diffusivity of water correlates with the number of hydrogen bonding sites within the channel, as is known for other sub-nm pore-size synthetic and biological water channels [Horner et al. Sci. Adv. 1:e1400083 (2015)].