CONSTRUCTION OF A DETAILED SEROTONINERGIC 5-HT2A RECEPTOR MODEL

We have been able to show that the most important 5-HT2a antagonists a nd agonists, belonging to chemically diverse classes can be fitted acc urately into a common pharmacophoric pattern. in this paper we make us e of the developed pharmacophore models to construct a fragmental amin o acid model reflecting binding properties and affinity data of the st ructures under study. The proposed fragment model is then superimposed onto the transmembraneous part of the 5-HT2a receptor. For this purpo se the helix coordinates from the known structure of bacteriorhodopsin serve as a matrix. New structures with high affinity for the 5-HT2a s ites were designed and their biological activities were predicted on t he basis of interaction energies calculated with the fragment model. T he predicted data show excellent agreement with experimental binding a ffinities.