Molecular modeling of ligand-receptor interactions in GABA C receptor.

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Osolodkin DI, Chupakhin VI, Palyulin VA, Zefirov NS

Molecular modeling of ligand-receptor interactions in GABA C receptor.

J Mol Graph Model. 2009 Apr;27(7):813-21. doi: 10.1016/j.jmgm.2008.12.004. Epub 2008 Dec 24.

PubMed ID

19167917 [ View in PubMed

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Abstract

A new homology model of the GABA binding site of the GABA(C) receptor was built. Natural agonist GABA and antagonist TPMPA were docked into the receptor and molecular dynamics simulation of the complexes was performed to clarify binding poses of the ligands. It was shown that orientation of the ligand is defined by salt bridges between the ligand and the arginine (Arg104) and glutamate residues (Glu194 and Glu196) of the binding site. Different behavior and binding poses for agonist and antagonist was demonstrated by molecular dynamics simulation along with differential movement of the loop C during agonist and antagonist binding. Binding orientations of the ligands revealed that main binding forces in the GABA binding site should be electrostatic ones.

DrugBank Data that Cites this Article

Drugs

TPMPA

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
TPMPA	Gamma-aminobutyric acid receptor subunit rho-1	Protein	Humans	Unknown	Antagonist	Details
TPMPA	Gamma-aminobutyric acid receptor subunit rho-2	Protein	Humans	Unknown	Antagonist	Details
TPMPA	Gamma-aminobutyric acid receptor subunit rho-3	Protein	Humans	Unknown	Antagonist	Details