TY - JOUR
T1 - Quantum chemical study of ligand-receptor electrostatic interactions in molecular recognition of the glutamate receptor
AU - Kubo, Minoru
AU - Shiomitsu, Eiji
AU - Odai, Kei
AU - Sugimoto, Tohru
AU - Suzuki, Hideo
AU - Ito, Etsuro
N1 - Funding Information:
This work was partly supported by a Grant-in-Aid for Research Fellowship (No. 14000230) of the Japan Society for the Promotion of Science for Young Scientists and the Sasakawa Scientific Research Grant from the Japan Science Society and the Junior Research Fellowship Grant from the Northern Advancement Center for Science and Technology to M.K., and by Grants-in-Aid (Nos. 11740246 and 13740261) from the Japan Society for the Promotion of Science to K.O., and by Grants-in-Aid (Nos. 13210006 and 15014201) for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan to E.I.
PY - 2003/9/5
Y1 - 2003/9/5
N2 - 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.
AB - 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.
KW - Aqueous condition
KW - Electrostatic potential
KW - GluR2
KW - Molecular orbital method
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U2 - 10.1016/S0166-1280(03)00368-3
DO - 10.1016/S0166-1280(03)00368-3
M3 - Article
AN - SCOPUS:0041375575
VL - 634
SP - 145
EP - 157
JO - Computational and Theoretical Chemistry
JF - Computational and Theoretical Chemistry
SN - 2210-271X
IS - 1-3
ER -