title: Docking of 6-chloropyridazin-3-yl derivatives active on nicotinic acetylcholine receptors into molluscan acetylcholine binding protein (AChBP).
abstract: The crystal structure of Acetylcholine Binding Protein (AChBP), homolog of the ligand binding domain of nAChR, has been used as model for computational investigations on the ligand-receptor interactions of derivatives of 6-chloropyridazine substituted at C3 with 3,8-diazabicyclo[3.2.1]octane, 2,5-diazabicyclo[2.2.1]heptane and with piperazine and homopiperazine, substituted or not at N4. The ligand-receptor complexes have been analyzed by docking techniques using the binding site of HEPES complexed with AChBP as template. The good relationship between the observed binding affinity and the calculated docking energy confirms that this model provides a good starting point for understanding the binding domain of neuronal nicotinic receptors. An analysis of the possible factors significant for the ligand recognition has evidenced, besides the cation-pi interaction, the distance between the chlorine atom of the pyridazinyl group and the carbonylic oxygen of Leu B112 as an important parameter in the modulation of the binding energy.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, Viale Abruzzi 42, 20131 Milano, Italy. roberto.artali@tiscali.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Artali
authors.forename: Gabriella
authors.initials: G
authors.lastname: Bombieri
authors.forename: Fiorella
authors.initials: F
authors.lastname: Meneghetti
mesh_terms: D000818:Animals; D001665:Binding Sites; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D019295:Computational Biology; D018360:Crystallography, X-Ray; D008024:Ligands; D008195:Lymnaea / Q000737:chemistry*; D008958:Models, Molecular; D011724:Pyridazines / Q000737:chemistry*; D011978:Receptors, Nicotinic / Q000737:chemistry*; D040681:Structural Homology, Protein
chemical_list: C428944:AChBP protein, Lymnaea; D001643:Bridged Bicyclo Compounds; D002352:Carrier Proteins; D008024:Ligands; D011724:Pyridazines; D011978:Receptors, Nicotinic