(a) A longitudinal section through the centre of the TWIK-1 channel at the end of the MD simulation. Left, a section of the average water density is overlaid. The S4 K+ ion is shown as a purple sphere. Note the hydrophobic nature residues lining the inner pore. Right, leucine residues contributing to the hydrophobic cuff are labelled. (b) Bottom-up view of the inner pore. Leu146 and Leu261 which form the hydrophobic cuff are shown as grey van der Waals spheres. M2 is shown in blue and M4 in orange.