CoMFA and homology-based models of the glycine binding site of N-methyl-D-aspartate receptor

I.G. Tikhonova, I.I. Baskin, V.A. Palyulin, N.S. Zefirov

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1609-1616
Number of pages8
JournalJournal of Medicinal Chemistry
Volume46
Issue number9
DOIs
Publication statusPublished - 24 Apr 2003

ASJC Scopus subject areas

  • Organic Chemistry

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