Interaction of CTX Lys27 side chain with the Kv1.2/2.1 K ⁺ channel selectivity filter. (A) Structure in K⁺ salt (PDB ID 4JTA) shows the S1 site in the selectivity filter occupied by the Lys27 ε-amino group. (B) Structure in Cs⁺ salt (PDB ID 4JTC) shows the S1 site occupied by a Cs⁺ ion instead of the Lys27 ε-amino group. (C) Representative conformation from an all-atom MD simulation of the 4JTA Kv channel structure, in which an outward transmembrane electric field of 500 mV was applied after equilibration. This frame was taken ∼10 ns after the application of the electric field to the protein–membrane complex. The red arrow indicates the direction of the electric field (only two subunits of the tetramer are shown). (D) Distance between the Lys27 ε-amino group and the center of mass of the four Kv1.2-Y373 carbonyl oxygens in the K⁺ and Cs⁺ structures. These data are compared with the average over a 10-ns time window, beginning 5 ns after the application of a 500-mV transmembrane electric field in an MD simulation (“500 mV Wobbling”). The error bar for the MD data represents the SD of the mean distance. 4JTA and 4JTC are creation by Banerjee et al. (2013). MD data were extracted from the CTX–Kv1.2 protein complex model used by Moldenhauer et al. (2019).