A theoretical study to investigate D2DAR/D4DAR selectivity: receptor modeling and molecular docking of dopaminergic ligands

J Med Chem. 2006 Feb 23;49(4):1397-407. doi: 10.1021/jm051046b.

Abstract

Molecular modeling methods have been applied to construct three-dimensional models for dopaminergic ligand complexes with D2 and D4 receptor subtypes (D2DAR and D4DAR), using the bovine rhodopsin crystal structure as a template for the modeling study. Different dopaminergic ligands, in particular the N-n-propyl-substituted 3-aryl- and 3-cyclohexylpiperidines, were docked into the D2DAR and the D4DAR, to evaluate the agreement between theoretical and experimental results as regards their D2/D4 selectivity. The different position of an aromatic region in the two receptors might explain the structural basis of this biological property.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cattle
  • Ligands
  • Models, Molecular*
  • Molecular Sequence Data
  • Piperidines / chemistry*
  • Receptors, Dopamine D2 / chemistry*
  • Receptors, Dopamine D4 / chemistry*
  • Rhodopsin / chemistry

Substances

  • Ligands
  • Piperidines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • Rhodopsin