Table 1. Aromatic ring stacking and hydrophobic interactions (HIA) between Y652 and F656 side chains and hERG antagonists in WT and Y652A mutant channels.
Compound | WT | Y652A | ||||
Y652 | F656 | ∑ HIA | A652 | F656 | ∑ HIA | |
Thioridazine | - | 3 (t,p,e) | 3 | - | 3 (t,p,e) | 3 |
Bepridil | 1 (p) | 1 (e) | 2 | - | 2 (e) | 2 |
Propafenone | 2 (t,e) | 2 (t,e) | 4 | - | 2 (e) | 2 |
GPV0009 | 3 (t,2e) | 1 (e) | 4 | - | 1 (e) | 1 |
Capsaicin | - | 1 (p) | 1 | - | 1 (e) | 1 |
Cisapride | 2 (p,e) | 2 (t,p) | 4 | - | - | 0 |
Dofetilide | 2 (t,e) | 2 (p,e) | 4 | - | 1 (e) | 1 |
E-4031 | 3 (t,2e) | 2 (e) | 5 | - | 2 (p,e) | 2 |
Ibutilide | 3 (e) | - | 3 | - | 1 (p) | 1 |
MK-499 | 1 (e) | 1 (e) | 2 | - | - | 0 |
Terfenadine | 3 (t,2e) | 2 (t,e) | 5 | - | 1 (e) | 1 |
(t = T-shaped stacking, p = parallel π-π-stacking, e = edge-to-edge interactions).