Figure 2. The S6 helices of Kv1.2_CH prefer to remain kinked.

(a) Schematic showing the extent of the motion of the S6 helices and how the S6 and pore coordinate systems are defined. The origin of each S6 coordinate system is defined as the position of the S6 helix in the Kvchim structure4. (b) The final converged (Supplementary Figure S4) 2D potential of mean force (PMF) showing how the free energy varies as the ends of the S6 helices of Kv1.2_CH are moved in the (x–y) plane of the membrane. The positions of the equivalent residues in the structures of Kv1.2 (ref. 3), closed KcsA (ref. 2) and MlotiK1 (ref. 60) are also plotted. The minimum free energy path (MFEP) between the centre of the well and the coordinates for KcsA is drawn. Six reference points are labelled; these are referred to in other panels of this figure as well as in other figures. Contours are drawn every 1 kcal mol⁻¹. (c) The conformation of the S6 helices (in red) when viewed intracellularly are shown. (d) The free energy increases along the MFEP, requiring 7.0 kcal mol⁻¹ per monomer to straighten the helices to the same extent as KcsA. The estimated errors are smaller than the filled squares and so are not plotted.