title: CoMFA and homology-based models of the glycine binding site of N-methyl-d-aspartate receptor.
abstract: Homology modeling was used to build 3D models of the N-methyl-d-aspartate (NMDA) receptor glycine binding site on the basis of an X-ray structure of the water-soluble AMPA-sensitive receptor. The docking of agonists and antagonists to these models was used to reveal binding modes of ligands and to explain known structure-activity relationships. Two types of quantitative models, 3D-QSAR/CoMFA and a regression model based on docking energies, were built for antagonists (derivatives of 4-hydroxy-2-quinolone, quinoxaline-2,3-dione, and related compounds). The CoMFA steric and electrostatic maps were superimposed on the homology-based model, and a close correspondence was marked. The derived computational models have permitted the evaluation of the structural features crucial for high glycine binding site affinity and are important for the design of new ligands.
authors.affiliation: Department of Chemistry, Moscow State University, Moscow 119992, Russia.
authors.forename: Irina G
authors.initials: IG
authors.lastname: Tikhonova
authors.forename: Igor I
authors.initials: II
authors.lastname: Baskin
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Palyulin
authors.forename: Nikolai S
authors.initials: NS
authors.lastname: Zefirov
mesh_terms: D001665:Binding Sites; D018690:Excitatory Amino Acid Agonists / Q000737:chemistry; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry; D005998:Glycine / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D015363:Quinolones / Q000737:chemistry; D011810:Quinoxalines / Q000737:chemistry; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry*; D012044:Regression Analysis; D017386:Sequence Homology, Amino Acid
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D015363:Quinolones; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine