title: Molecular dynamics study of 4-OH-phenylacetyl- D-Y(Me)FQNRPR-NH2 selectivity to V1a receptor.
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.
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. lukasz@chem.univ.gda.pl
authors.forename: Artur
authors.initials: A
authors.lastname: Giełdoń
authors.forename: Rajmund
authors.initials: R
authors.lastname: Kaźmierkiewicz
authors.forename: Rafał
authors.initials: R
authors.lastname: Slusarz
authors.forename: Marta
authors.initials: M
authors.lastname: Pasenkiewicz-Gierula
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ciarkowski
mesh_terms: D003198:Computer Simulation; D006801:Humans; D006878:Hydroxides / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D018045:Receptors, Oxytocin / Q000737:chemistry*; D017483:Receptors, Vasopressin / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D006878:Hydroxides; D008024:Ligands; D010455:Peptides; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; C031356:hydroxide ion