Molecular modelling studies on the digitalis binding site of the Na+/K(+)-ATPase.

Using molecular modelling methods, several digitalis-unlike compounds such as chlormadinol acetate and cassaine, which bind to the digitalis receptor and inhibit the Na+/K(+)-ATPase were compared with cardenolides as a standard. The interaction energies of this group of compounds with various probes such as a methyl group or a NH-amid group were calculated using GRID and compared using GRAD. A pharmacophore model was derived, which describes all corresponding inotropic substrates. On this basis and including experimental knowledge on the Na+/K(+)-ATPase a receptor model was developed.