(A) nhTMEM16 is shown as a molecular surface (extracellular side up) colored by residue type (blue, basic; red, acidic; green, polar; white, nonpolar) in a phospholipid bilayer composed of POPC and POPS. The initial (t = 0) distribution of phospholipids is shown by the tan spheres representing lipid phosphorus atoms. At the end of the 1000-ns MD simulation, the average phospholipid phosphate density within 10 Å of the protein during the Ca2+-activated simulation is shown as an orange surface outlined by black lines that is contoured at 7.5% of the bulk phosphate density. Two different views (rotated by 90° around the membrane normal) are shown, with one of the aqueducts visible in the right panel. (B) Number of phosphorus atoms within 10 Å of the protein that enter the 25 Å- (blue curve) or 20 Å- (red curve) thick core region of the membrane, as defined by the blue and red areas in panel (C). (C) Distribution of phosphorus atoms along the membrane z axis at t = 0 (black curve), t = 80 ns (green curve, corresponding to vertical green bar in panel (B)), and t = 480 ns (orange curve, corresponding to vertical orange bar in panel (B)).