The role of electrostatic interaction in the molecular recognition of selective agonists to metabotropic glutamate receptors

Proteins. 2003 Mar 1;50(4):609-19. doi: 10.1002/prot.10301.

Abstract

The influence of electrostatic interactions in determining selectivity for individual subtypes of metabotropic glutamate receptors (mGluRs) is evaluated for a small set of agonists by using the program Delphi and the information thus obtained is compared with docking experiments carried out with AutoDock. The evaluation of the electrostatic component of the free energy of binding for L-Glu, L-AP4, or S-PPG to mGluR1, mGluR2, and mGluR4 subtypes allowed for the detection of subtle differences in the electronic properties of the three subtypes, differences that can account for the observed agonist selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Glutamic Acid / chemistry
  • Glutamic Acid / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / metabolism
  • Propionates / chemistry
  • Propionates / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Metabotropic Glutamate / agonists*
  • Receptors, Metabotropic Glutamate / chemistry*
  • Receptors, Metabotropic Glutamate / metabolism
  • Sequence Alignment
  • Static Electricity

Substances

  • 2-amino-4-phosphono-propinate
  • Organophosphorus Compounds
  • Propionates
  • Receptors, Metabotropic Glutamate
  • S-PPG compound
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor type 1
  • Glutamic Acid
  • metabotropic glutamate receptor 4