Docking of hydroxyzine within the inner cavity of a HERG channel homology model. (A) The major microspecies of hydroxyzine protonation at pH 7.4. (B) Inner view of hydroxyzine docked to the ligand binding site in the HERG channel. Hydroxyzine is shown in stick form and the dotted line indicates a hydrogen bond between the blocker and channel. The HERG channel inhibitor hydroxyzine shows interactions with THR623 (subunit A) and TYR652 (subunit C). (C) PoseView analysis of protein-ligand interactions. Hydrogen bonding is depicted as a dotted line between the participating atoms. The green lines with residue names and numbers indicate hydrophobic interactions between the drug and channel. Note the hydrogen bond between the hydrogen atom of the protonated nitrogen (in the hydroxyzine molecule) and the carbonyl oxygen atom of THR623(I).