Quantum chemical study of ligand-receptor electrostatic interactions in molecular recognition of the glutamate receptor

Minoru Kubo, Eiji Shiomitsu, Kei Odai, Tohru Sugimoto, Hideo Suzuki, Etsuro Ito

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6 Citations (Scopus)

Abstract

To understand the mechanism of molecular recognition of glutamate receptors, we calculated the dipole moments, net charges, and electrostatic potentials of the agonists and antagonists of the glutamate receptors under aqueous conditions by the ab initio molecular orbital method at the HF/6-311++G(3df,2pd) level. All of the ligands had negative net charges at both termini and, consequently, formed negative electrostatic potentials at these termini. We further calculated the net charges and electrostatic potential of the S1S2 lobes of the glutamate receptor subunit GluR2 under aqueous conditions by the semiempirical PM3 molecular orbital method, and found that the ligand-binding cleft of the S1S2 lobes formed a primarily positive electrostatic potential. A strongly positive electrostatic potential was formed particularly around Arg485 in the S1 lobe. A negative electrostatic potential was observed only in a small region around Glu657 in the S2 lobe in the ligand-binding cleft. When a ligand approaches the ligand-binding cleft, it may proceed to Arg485 in the S1 lobe, due to both repulsion by the negative electrostatic potential of Glu657 as well as the attraction of the strongly positive electrostatic potential of Arg485 itself.

Original languageEnglish
Pages (from-to)145-157
Number of pages13
JournalJournal of Molecular Structure: THEOCHEM
Volume634
DOIs
Publication statusPublished - 2003 Sep 5
Externally publishedYes

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Keywords

  • Aqueous condition
  • Electrostatic potential
  • GluR2
  • Molecular orbital method

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computational Theory and Mathematics
  • Atomic and Molecular Physics, and Optics

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