Figure 8: Constrained docking of AC-10 to Kv7.1 channel.

(a) AC-10 carbene docked by constraining the distance (2 ±1 Å) to the KCNE1 Thr58 side chain. The energy minimized model complex is shown. Kv7.1/KCNE1 was surface rendered, cut in the middle and colored blue, KCNE1 Thr58 is presented in ball-representation and CPK color coding with carbons in cyan. Compound AC-10 is shown in ball-representation and standard CPK color coding. K⁺-ions are shown as yellow spheres. (b) Close-up of AC-10 in its binding pocket. (c) Close-up representation of similar region, but with protein shown as ribbons (KCNE1 in magenta, Kv7.1 subunits in yellow green orange). (d) The AC binding site is formed by several residues that surround a tunnel-like structure (fenestration) that bridges the inner cavity (left) and the membrane (right). The surface lining the fenestration is hydrophobic, especially in the region around the adamantine of AC-1. (e) The specific ligand-receptor interactions determined using Discovery Studio 4.0. are: six alkyl interactions (pink), one alkyl-pi interaction (pink) and one carbon interaction (green).