Water access to the side chains of E203 and E148 upon perturbation of ClC-ec1 along the seventh NM, viewed from within the membrane. The side chains of E203, Y445, S107, E148, and R147 are explicitly shown. Two Cl− ions (1 and 2) are shown in the central and inner binding sites as intermediate-sized spheres. Traces of overlapping cross-hatched spheres illustrate water access from the cytoplasm to the E203 and from the periplasm to the E148. (A) Minimized ClC-ec1 corresponding to the crystal structure. (B and C) “Positive” and “negative” perturbation along the seventh all-atom NM. Black arrows indicate the direction of the intracellular pore tilt. The figure is drawn using VMD.