(A) Representative structure of transmembrane helices 4, 10 and 11 for protomer I (cyan) of system 1 at image 5 drawn with cartoons. Deprotonated/protonated D408, K940 and R971 are represented by spheres. Averaged electrostatic potential isosurfaces are drawn in blue (corresponding to the isovalue of 0.06 kcal/mol) and red (−0.06 kcal/mol). (B) After transforming the protonation state toward system 2. (C) System 2 at image 15. For comparison, the helices of image 5 are drawn in gray. (D) 2500 snapshots of water atoms are drawn with red points (oxygen) and white points (hydrogen) for protomer I of system 1 at image 5. Key residues (L400, D924, T933, L937, K940, F982 and R971) are drawn with spheres. (E) System 2 at image 15. For comparison, the helices of image 5 are drawn in gray.