Fig. 7. An open state model of the TMEM175 channel. (A) An open state model structure of the TMEM175 channel was developed by the expansion of two van der Waals spheres (blue circle; upper panel) placed within the gating constriction of the pore. The upper panel shows the ILL motif sidechains (cyan) of the crystal structure; the lower panel shows the same region after pore expansion followed by 10 ns relaxation. (B) The simulation of water molecules (red and white) within the transmembrane pore (blue) of the open state model of TMEM175. Initially (t = 1 ns) the pore is de-wetted. Shortly after (t = 2 ns) the pore is wetted and remains so for the remainder of the simulation. (C) The pore radius profile in the region of the hydrophobic gate for the crystal structure of TMEM175 (grey), for the expanded pore (blue) and for the open state model (black) at the end of a 100 ns unrestrained simulation (see text for details). (D) The position of water molecules (pale blue circles) along the pore axis for the hydrophobic constriction of the TMEM175 pore in the closed state (i.e. the X-ray structure). The pore can be seen to be de-wetted for most of the simulation. (E) The positions of water molecules (pale blue circles) and K⁺ ions (purple circles) along the pore axis of the open state model of the TMEM175 pore. The pore can be seen to be wetted throughout the simulation with the entry and exit of K⁺ ions into and out of the pore.