Molecular dynamics study of 4-OH-phenylacetyl- D-Y(Me)FQNRPR-NH2 selectivity to V1a receptor

J Mol Model. 2003 Dec;9(6):372-8. doi: 10.1007/s00894-003-0142-0. Epub 2003 Oct 7.

Abstract

G protein-coupled receptors relay diverse extracellular signals into cells via a common mechanism, involving activation of cytosol G proteins. The mechanism underlies the actions of approximately 50% of all drugs. In this work, we focus on simulating three protein-ligand complexes of the neurohypophyseal hormone analog 4-OH-phenylacetyl- D-Y(Me)FQNRPR-NH2 (I) with the human V1a, V2 and oxytocin receptors. The peptideI is a potent selective V1a receptor antagonist. To obtain relaxed models of the complexes, the following techniques were used: docking ofI into the vasopressin V1a, V2 and oxytocin receptor models, optimization of the geometry of the resulting complexes and molecular dynamics in a fully hydrated 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphatidylcholine lipid bilayer. The results of the simulations allow us to draw some conclusions about the ligand selectivity to V1aR.

MeSH terms

  • Computer Simulation
  • Humans
  • Hydroxides / chemistry*
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Peptides / chemistry*
  • Receptors, Oxytocin / chemistry*
  • Receptors, Vasopressin / chemistry*
  • Structure-Activity Relationship

Substances

  • Hydroxides
  • Ligands
  • Peptides
  • Receptors, Oxytocin
  • Receptors, Vasopressin
  • hydroxide ion