Modelling drugs and receptors using potentials: examples in the GPCRs' domain

Shape complementarity, electrostatic and hydrophobic matching, were used to model drugs and receptors. From known experimental data on alpha1A/alpha2A-adrenergic ligands and alpha1A/alpha2A-adrenoceptors, a model for the ligand binding sites, based on the structure of bacteriorhodopsin as a template, was proposed and built. Agonists and antagonists have overlapping but different binding sites. Emphasis was given on the role of the disulphide bridge and on the role of the sodium site. The model was extended to other G-protein coupled receptors.