We generated 50 independent low energy Na v 1.7 conformations using the ROSETTA package. This was done by running the backrub algorithm first to create 50 uncorrelated backbone conformations. The backrub algorithm rotates the protein backbone as a static body about the carbon alpha (C α ) and we selected the low energy structure out of 10, 000 trials for each conformation. We then ran the fixbb algorithm to repack the side chains for each selected backbone conformation. Fixbb is a Monte Carlo method that samples the Dunbrack backbone-dependent rotamer library. As a result, these 50 structures make a conformational ensemble that span the timescale required to pivot the backbone along the C α s and switch side chain rotamers. NMR J-coupling experiments have quantified that such side chain conformational transitions occur on timescales of nanoseconds to microseconds. The 50 conformers were embedded into a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) membrane bilayer and solvated in 0.15M NaCl solution using the Membrane Builder of CHARMM-GUI webserver.