A theoretical study to investigate D2DAR/D4DAR selectivity: receptor modeling and molecular docking of dopaminergic ligands.
Molecular modeling methods have been applied to construct three-dimensional models for dopaminergic ligand complexes with D2 and D4 receptor subtypes (D2DAR and D4DAR), using the bovine rhodopsin crystal structure as a template for the modeling study. Different dopaminergic ligands, in particular the N-n-propyl-substituted 3-aryl- and 3-cyclohexylpiperidines, were docked into the D2DAR and the D4DAR, to evaluate the agreement between theoretical and experimental results as regards their D2/D4 selectivity. The different position of an aromatic region in the two receptors might explain the structural basis of this biological property.
Ortore
Gabriella
G
Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno 6, 56126 Pisa, Italy.
Tuccinardi
Tiziano
T
Bertini
Simone
S
Martinelli
Adriano
A
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010880:Piperidines / Q000737:chemistry*; D017448:Receptors, Dopamine D2 / Q000737:chemistry*; D050638:Receptors, Dopamine D4 / Q000737:chemistry*; D012243:Rhodopsin / Q000737:chemistry
D008024:Ligands; D010880:Piperidines; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D012243:Rhodopsin