Correlation between inner gate opening and local conformational rearrangement of Phe103, Ile100, and Thr74. (A and B) Critical conformational difference between partially (A) and fully (B) open structure for the transmembrane helices and the selectivity filter. (C–H) Probability densities of three ensembles, respectively, were determined by combining several trajectories started from three crystal structures, i.e., two trajectories (Traj-9 and -10) started from 3FB5 (green), three trajectories (Traj-6–8) from 3FB6 (blue), and four trajectories (Traj-1–4) from 3F7V (red), to represent the opening degrees from partially to fully open of the inner gate. The probability density functions of these Cα-atom distances and rotamers were estimated by using kernel density estimation based on the sample distributions. In C, D, and F, the histograms correspond to the distances, i.e., T112-T112, T74-I100, and I100-F103, between adjacent subunits (as opposed to diagonally opposed cross-subunit distance discussed used elsewhere) because they yield a clearer picture for the allosteric coupling due to the key inter-subunit contacts from adjacent subunits.