title: Different binding modes of structurally diverse ligands for human D3DAR.
abstract: Five different dopamine D3 receptors (D3DARs) models were created considering some suggested binding modes for D3DAR antagonists reported in earlier computational studies. Different hypotheses are justified because of the lack of experimental information about the putative site of interaction and are also due to the variability in scaffolds and size of D3DAR ligands. In this study 114 potent and selective D3DAR antagonists or partial agonists are used as key experimental information to discriminate the most reliable receptor model and to build a docking based 3D quantitative structure-activity relationship model able to indicate the ligand properties and the residues important for activity. The ability of this D3DAR model to discriminate the binding mode of different classes of ligands, showing a good quantitative correlation with their activity, encourages us to use it for screening novel lead compounds.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno 6, 56126 Pisa, Italy. ortore@farm.unipi.it
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ortore
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Orlandini
authors.forename: Adriano
authors.initials: A
authors.lastname: Martinelli
mesh_terms: D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D014584:User-Computer Interface
chemical_list: D008024:Ligands; D050637:Receptors, Dopamine D3