Channel deactivation in the absence of PIP ₂ . (A) Channel deactivation and activation gate closure measured by the C_α–C_α diagonal distance at gate residues I177 and M181 (Sim. 13, top), and number of pore cavity water molecules and CTD-SF center of mass separation (Sim. 13, bottom). (B) Intracellular view of the inner helix, TM2, and IH in the presence and absence of PIP₂ (blue, Sim. 4; yellow, Sim. 13), superposed with the PIP₂-depleted, apo Kir2.2 crystal structure (red, PDB ID 3JYC), with an SF-bound potassium ion in magenta and the C, N, and O atoms of the SF residues shown in gray, blue, and red, respectively. (C) Closest atomic distances (per monomer) between any of the TM2 residues of the R/K-rich region (R186:Nζ, K188:Cζ, K189:Cζ, or R190: Nζ) and each of the following residues: (i) E304:Cδ of the G-loop, (ii) D76:Cγ, and (iii) D69:Cγ of the IH. The distance in each monomer is colored individually and the conformation of the channel is indicated by Open and Closed. (D) Simulation snapshots revealing proximity between TM2 residues R186, K188, K189, and R190 (gray), and PIP₂ in the open state (left), and between IH residues D69 and D76 and the R/K-rich region in the absence of PIP₂ (right). (E) Distributions of the CTD R219:Nζ/K220:Cζ–POPS:P distance (per subunit) indicating an altered interaction pattern before and after pore closure and channel deactivation.