More specifically, we report that Asp-361, Glu-927 and Lys-1406, from the selectivity filter, contributes -3.41, -5.28 and -1.39 MV/cm to the projected electric field, respectively. Further, Glu-927 and Lys-1406 exhibit large standard deviation, exceeding 10 MV/cm, suggesting that their action is highly sensitive to their precise orientation within the pore cavity. This contrasts with Arg-922 whose standard deviation is 1.68 MV/cm despite a field magnitude over 4 MV/cm. In Figure ) and 3c), we show the time evolution of E O pw O pw proj with that of the χ dihedral angles characterizing the side chain conformation of Lys-1406 and Arg-922 (the rotamer analysis for other residues is provided in Supporting Information). We see that large changes in the magnitude of E O pw O pw proj , yielding high standard deviations, correlates with changes in χ, suggesting that the electrostatic environment in Na v 's pore is tightly controlled by the precise conformation of key residues in and near the selectivity filter region.