title: Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model.
abstract: Interest in structure-based G-protein-coupled receptor (GPCR) ligand discovery is huge, given that almost 30 % of all approved drugs belong to this category of active compounds. The GPCR family includes the dopamine receptor subtype D2 (D2DR), but unfortunately--as is true of most GPCRs--no experimental structures are available for these receptors. In this publication, we present the molecular model of D2DR based on the previously published crystal structure of the dopamine D3 receptor (D3DR). A molecular modeling study using homology modeling and docking simulation provided a rational explanation for the behavior of the arylpiperazine ligand. The observed binding modes and receptor-ligand interactions provided us with fresh clues about how to optimize selectivity for D2DR receptors.
authors.affiliation: ICTM-Centre for Chemistry, University of Belgrade, Njegoseva 12, 11000 Belgrade, Serbia. vladimir.sukalovic@abcsistem.rs
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sukalovic
authors.forename: Vukic
authors.initials: V
authors.lastname: Soskic
authors.forename: Milan
authors.initials: M
authors.lastname: Sencanski
authors.forename: Deana
authors.initials: D
authors.lastname: Andric
authors.forename: Sladjana
authors.initials: S
authors.lastname: Kostic-Rajacic
mesh_terms: D001665:Binding Sites; D004298:Dopamine / Q000737:chemistry*; D018492:Dopamine Antagonists / Q000737:chemistry*; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D010879:Piperazines / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017448:Receptors, Dopamine D2 / Q000737:chemistry*; D050637:Receptors, Dopamine D3 / Q000737:chemistry*; D040681:Structural Homology, Protein
chemical_list: D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D004298:Dopamine