Figure 3

Systematic search for the energetically optimal binding site of correolide in model 2/4. A, Ligand-receptor energy of correolide pulled through the pore. The zero translational position is calibrated to show the complex with an oxygen atom of correolide bound to the K+ ion in position 4. Blue and green lines represent trajectories with the epoxy group oriented towards and away from the selectivity filter, respectively. B, Contributions of K+ ions and correolide-sensing residues revealed by Hanner et al. [15] to the interaction energy of correolide oriented with its epoxy group away from the selectivity filter. Also included is the contribution of Ile⁴²⁰ whose mutation to Ala affected the channels expression. The contributions of amino acids are summed over four subunits. The energy values are partitioned from the MC-minimized structures at specific translational positions. In most of the translational positions around the selectivity filter, the sum of six monitored contributions is close to the total ligand-receptor energy indicating that the contribution of other residues is small. At the cytoplasmic entrance to the open pore, residues Val⁴²⁸ and Asn⁴³² contribute energy to correolide binding. C and D, The side and cytoplasmic views of superposed MC-minimized complexes at different translational positions with the 7-membered ring facing the selectivity filter. Displacement of the K+ ion from the pore axis occurs at the high-energy leftmost points of the profile (A, B) where correolide is forced into the selectivity filter.