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.
Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno 6, 56126 Pisa, Italy.
Gabriella
G
Ortore
Tiziano
T
Tuccinardi
Simone
S
Bertini
Adriano
A
Martinelli
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