MCM trajectory for a sodium ion (small yellow spheres) pulled from the selectivity filter in the extracellular direction. (A) Ion positions in the complex of Nav1.4 with GIIIA, which produces a complete block. The trajectory is interrupted by R13 residue. (B) Ion positions in the complex of Nav1.4 with GIIIA mutant R13A, which produces a partial block. The trajectory is smooth. (C) Energy of the ion-system interactions. For the wild-type toxin, but not its mutant, the energy plot has a region of positive (repulsive) energies.