Modeling of ligand binding to dopamine D2 receptor

• Main Authors: Ostopovici-Halip Liliana, Rad-Curpan Ramona
• Format: Article
• Language: English
• Published: Serbian Chemical Society 2014-01-01
• Series: Journal of the Serbian Chemical Society
• Subjects: GPCR; homology modeling; D2 receptor; molecular docking
• Online Access: http://www.doiserbia.nb.rs/img/doi/0352-5139/2014/0352-51391300046O.pdf
• ISSN: 0352-5139; 1820-7421

The dopaminic receptors have been for long time the major targets for developing new small molecules with high affinity and selectivity to treat psychiatric disorders, neurodegeneration, drug abuse, and other therapeutic areas. In the absence of a 3D structure for the human D2 dopamine (HDD2) receptor, the efforts for discovery and design of new potential drugs rely on comparative models generation, docking and pharmacophore development studies. To get a better understanding of the HDD2 receptor binding site and the ligand-receptor interactions a homology model of HDD2 receptor based on the X-ray structure of β2-adrenergic receptor has been built and used to dock a set of partial agonists of HDD2 receptor. The main characteristics of the binding mode for the HDD2 partial agonists set are given by the ligand particular folding and a complex network of contacts represented by stacking interactions, salt bridge and hydrogen bond formation. The characterization of the partial agonist binding mode at HDD2 receptor provide the needed information to generate pharmacophore models which represent essential information in the future virtual screening studies in order to identify new potential HDD2 partial agonists.