title: [The role of stacking interactions in the mechanisms of binding of the glycine site of NMDA-receptor with antagonists and 3-hydroxykynurenine].
abstract: Ab initio quantum chemical calculations of benzene dimer, benzene dimer with 5,7 clorination of one aromatic ring, 3-hydroxykynurenine, and kunurenic acid molecules situated above Phe484 aromatic ring of receptor binding site fragment were carried out in order to investigate the role of stacking interaction in the binding of agonists and antagonists with the glycine site of the NMDA receptor NR1 subunit. All calculations were done with the help of GAMESS 6.4 software with 6-31G** atomic gaussian basal functions with complete optimization of geometry and taking into account the electron correlation up to the second-order Moller-Plesset perturbation theory. It was shown that the parallel dislodged conformations of the benzene dimer is energetically most advantageous. Successive substitution of chlorine atoms for the protons of one aromatic ring in 7 and 5 positions leads to an increase in stacking-interaction energy and a mutual displacement of aromatic rings. In the case of kunurenic acid and its derivatives, which are NMDA receptor antagonists, the increase in the energy of stacking interactions leads to the strengthening of inhibition of the ion channel, whereas the 3-hydroxykynurenine molecule is neither agonist, nor antagonist for the glycine site of the NMDA receptor due to the sterical constraints.
authors.forename: G A
authors.initials: GA
authors.lastname: Zakharov
authors.forename: A V
authors.initials: AV
authors.lastname: Popov
authors.forename: E V
authors.initials: EV
authors.lastname: Savvateeva-Popova
authors.forename: B F
authors.initials: BF
authors.lastname: Shchegolev
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry; D001665:Binding Sites; D019281:Dimerization; D005998:Glycine / Q000737:chemistry*; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011789:Quantum Theory; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D001555:Benzene Derivatives; D005998:Glycine; D007736:Kynurenic Acid; D007737:Kynurenine; D016194:Receptors, N-Methyl-D-Aspartate; C005045:3-hydroxykynurenine