Theoretical models of interactions between buspirone analogues and 5-HT1A and 5-HT2A serotonin receptor subtypes

In present study the structure-selectivity relationship of buspirone and six of its analogues towards 5-HT1A and 5-HT2A serotonin receptors was investigated on molecular level. Molecular mechanics energy minimisation and advanced molecular dynamics (MD) simulations allowed us to perform a dynamic structural analysis of transmembrane helical domains of the human 5-HT1A and 5-HT2A receptors and investigate the ligand-induced changes of the entire structure of the ligand-receptor complex. The obtained results suggest, that helical and extracellular domains of both receptors have different topography of the putative binding sites and also different dynamical behaviour. The results of this study are consistent with experimental site-directed mutagenesis data and binding affinities of examined ligands towards both serotonin receptors.