For further analysis, we list in Table the top contributors to the projected electric field. A top contributor is a residue whose signal in Figure is over 4 MV/cm in absolute magnitude and/or standard deviation. In complement to Figure , we provide in Supporting Information a plot of the field magnitude as a function of standard deviation for each residue. Nine out of the twelve residues listed in Table are located on the P-loops that connect helices S5 and S6 in each domain. Previous literature highlighted the importance of these P-loops for channel selectivity. Therefore, we find that residues critical to channel selectivity generate significant electric fields in the pore of Nav1.7. These residues are located close to the selectivity filter (Figure ), while only three are close to the inactivation gate, despite Na v 1.7 being in its inactivated state in our simulations. This implies that Na v 1.7 is preorganized with residues responsible for Na + binding to the selectivity filter region generating electric fields regardless of the state of the channel, and without the influence of an external bias. . A top contributor is a residue whose signal is over 4 MV/cm in magnitude and/or standard deviation. The error is calculated as the error of the mean over the conformational ensemble.