Figure 1

Structure of correolide. A, Chemical formula. B, Constraints used to pull correolide along the pore axis in the orientation with the epoxy group towards the selectivity filter. The inner pore is shown schematically by the thick line. K+ ion in position 4 of the selectivity filter is shown as a sphere. A dot-designated driven atom of correolide shared by two 6-membered rings was constrained to plane 1, which is normal to the pore axis. The co-driven dot-designated atom shared by 6- and 7-membered rings was constrained between planes 2 and 3, which are farther from the selectivity filter than plane 1. All three planes were concertedly moved with the step of 0.5 Å normally to the pore axis, and at each step the energy of the complex was MC-minimized. The driven atom retains two of the three degrees of freedom, while co-driven atom retains all three degrees of freedom, but cannot occur ahead of the driven atom. Overall, the ligand retains all internal degrees of freedom and five out of six rigid-body degrees of freedom. The curved arrows show that the correolide can turn around the pore axis and its long axis can decline significantly from the pore axis, but the ligand cannot flip-flop. A similar system of constraints was used to move correolide with its 7-membered ring towards the selectivity filter.