A model of the serotonin 5-HT1A receptor: agonist and antagonist binding sites

We built a model for the 5-HT 1A receptor, using the 3D-structure of bacteriorhodopsin as a structural template. With the use of site-directed mutagenesis data, several potent 5-HT 1A agonists, belonging to five different structural classes, and an aryloxypropanolamine antagonist, were docked into the receptor model. After docking, the surrounding of the ligands appeared to be in full agreement with previously reported SAR-data of 5-HT 1A ligands. In this study, for the first time, an explanation for 5-HT SAR results is given in terms of interactions between ligands and amino acid residues. Also the selectivity of 8-OH-DPAT for the 5-HT 1A receptor is accounted for. In our model the agonists and the antagonist interact with different residues on several helices