PIP ₂ increased coupling between the TMD and CTD within a subunit. (a) Magnified ribbon diagrams of Kir2.2 channels, focused on the interface between the TMD and CTD, are colored by the correlation coefficients with the reference residue 177 for the simulations without PIP₂ (left) or with PIP₂ (right). Subunit A and C are colored by the Intra coefficients, and B and D by the Inter coefficients. Subunit A is closest and shown in opaque ribbons, and subunit C in the back is omitted for clarity. Subunit B and D are shown with transparent ribbons, and the Cα atoms of I177 and M181 of subunit B and D are marked by spheres and two arrows. M308 residues, forming the G-loop, are also marked by spheres with the filled arrowhead indicating subunit A and the open arrowhead subunit B. The color bar shows the color range for the coefficients. (b) Schematic diagrams of Kir2 channel tetramer showing the spatial organization among the four subunits with staggered interactions between each TMD and the CTD of the neighboring subunit. The boxes indicating each TMD or CTD domain are colored with the vertical trends of cross-correlation coefficients for the Intra (Subunit A and C) and Inter (Subunit B and D) conditions. The approximate locations of the two gates are indicated.