title: Studying the catechol binding cavity in comparative models of human dopamine D2 receptor.
abstract: Obtaining more structural information of human dopamine D(2) receptor may help in the design of better therapeutic agents against diseases such as Parkinson. In this study attempts have been made to develop a functional model for the catechol binding site of the human dopamine D(2) receptor, with two primary models being postulated based on the presence of a disulfide bridge in the second extracellular loop. The models have been subjected to subsequent molecular dynamics simulation and receptor based virtual screening of catechol structures. During steady state of the simulations, representative models with the reduced disulfide bridge were more capable of discriminating between active and inactive catechol structures. It is postulated that similar conformational changes of the second extracellular loop observed in 5-HT4 and β-adrenergic receptors, might also take place in the human D(2) receptor during its interaction with agonist ligands.
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland. asakhteman@razi.tums.ac.ir
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sakhteman
authors.forename: Maija
authors.initials: M
authors.lastname: Lahtela-Kakkonen
authors.forename: Antti
authors.initials: A
authors.lastname: Poso
mesh_terms: D000595:Amino Acid Sequence; D019540:Area Under Curve; D001665:Binding Sites; D002396:Catechols / Q000737:chemistry* / Q000378:metabolism*; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017448:Receptors, Dopamine D2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D002396:Catechols; D004220:Disulfides; D017448:Receptors, Dopamine D2