Figure 10.

Comparison of the ion translocation PMF obtained through different umbrella sampling approaches: (a) 2D umbrella sampling calculation with 154 windows covering the whole conformational space (regions above 10 kcal/mol are not detailed). (b) Result of the 2D self-learning umbrella sampling calculation using a total of 63 windows. (c–d) 2D projection (c) of a 3D PMF (d) calculated with 385 windows generated by the self-learning approach. The reaction coordinates in panels (a) to (c) are as described in Figure 9. In the 3D PMF presented in (d), each ion is considered separately $W\left[K_z^1,K_z^2,K_z^3\right]$, with $K_Z^2$ sticking out of the plane.