GIIIA in Nav1.4 models. (A) Different orientation of the outer carboxylates (sticks) in the NavAb-based models with the straightforward (magenta) and adjusted (green) sequence alignments. P1 helices are shown as ribbons. Selectivity-filter region and P2 helices are shown as thin rods. (B) Lowest-energy GIIIA-binding modes obtained in the models based on the straightforward (yellow) and adjusted (orange) alignments. (C and D) Correlation between energies of pairwise interactions in experiments (Table 1) and the models, which are based on the straightforward (C) and adjusted (D) sequence alignments. Contacts, which were used in docking procedure, have blue labels. Other contacts have magenta labels. (E) Asymmetric binding of GIIIA. The toxin body (orange) is shifted toward repeat III. (F) Ensemble of predicted orientations of side chains of key basic residues of GIIIA. Dark green, red, light green, orange, and cyan dots show the centers of the charged moieties in K9, K11, R13, K16, and R19, respectively.