Molecular dynamics study of 4-OH-phenylacetyl- D -Y(Me)FQNRPR-NH 2 selectivity to V1a receptor

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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 ~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 peptide I is a potent selective V1a receptor antagonist. To obtain relaxed models of the complexes, the following techniques were used: docking of I 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.