The 3D structure of the binding pocket of the human oxytocin receptor for benzoxazine antagonists, determined by molecular docking, scoring functions and 3D-QSAR methods

Balázs Jójárt, T. Martinek, A. Márki

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Molecular docking and 3D-QSAR studies were performed to determine the binding mode for a series of benzoxazine oxytocin antagonists taken from the literature. Structural hypotheses were generated by docking the most active molecule to the rigid receptor by means of AutoDock 3.05. The cluster analysis yielded seven possible binding conformations. These structures were refined by using constrained simulated annealing, and the further ligands were aligned in the refined receptor by molecular docking. A good correlation was found between the estimated Delta;Gbind and the pKi values for complex F. The Connolly-surface analysis, CoMFA and CoMSIA models qCoMFA 2 = 0.653, qCoMSA2 = 0.630 and rpred,CoMFA2 = 0.852, rpred,CoMSIA 2 = 0.815) confirmed the scoring function results. The structural features of the receptor-ligand complex and the CoMFA and CoMSIA fields are in closely connected. These results suggest that receptor-ligand complex F is the most likely binding hypothesis for the studied benzoxazine analogs.

Original languageEnglish
Pages (from-to)341-356
Number of pages16
JournalJournal of Computer-Aided Molecular Design
Volume19
Issue number5
DOIs
Publication statusPublished - May 2005

Fingerprint

Benzoxazines
Quantitative Structure-Activity Relationship
scoring
Ligands
ligands
Surface analysis
Cluster analysis
Oxytocin
Simulated annealing
cluster analysis
Cluster Analysis
Conformations
simulated annealing
Molecules
analogs
human OXTR protein
molecules

Keywords

  • 3D-QSAR
  • AutoDock
  • Benzoxazine
  • Binding mode
  • Binding pocket
  • Oxytocin receptor
  • Scoring function

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

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abstract = "Molecular docking and 3D-QSAR studies were performed to determine the binding mode for a series of benzoxazine oxytocin antagonists taken from the literature. Structural hypotheses were generated by docking the most active molecule to the rigid receptor by means of AutoDock 3.05. The cluster analysis yielded seven possible binding conformations. These structures were refined by using constrained simulated annealing, and the further ligands were aligned in the refined receptor by molecular docking. A good correlation was found between the estimated Delta;Gbind and the pKi values for complex F. The Connolly-surface analysis, CoMFA and CoMSIA models qCoMFA 2 = 0.653, qCoMSA2 = 0.630 and rpred,CoMFA2 = 0.852, rpred,CoMSIA 2 = 0.815) confirmed the scoring function results. The structural features of the receptor-ligand complex and the CoMFA and CoMSIA fields are in closely connected. These results suggest that receptor-ligand complex F is the most likely binding hypothesis for the studied benzoxazine analogs.",
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AU - Márki, A.

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N2 - Molecular docking and 3D-QSAR studies were performed to determine the binding mode for a series of benzoxazine oxytocin antagonists taken from the literature. Structural hypotheses were generated by docking the most active molecule to the rigid receptor by means of AutoDock 3.05. The cluster analysis yielded seven possible binding conformations. These structures were refined by using constrained simulated annealing, and the further ligands were aligned in the refined receptor by molecular docking. A good correlation was found between the estimated Delta;Gbind and the pKi values for complex F. The Connolly-surface analysis, CoMFA and CoMSIA models qCoMFA 2 = 0.653, qCoMSA2 = 0.630 and rpred,CoMFA2 = 0.852, rpred,CoMSIA 2 = 0.815) confirmed the scoring function results. The structural features of the receptor-ligand complex and the CoMFA and CoMSIA fields are in closely connected. These results suggest that receptor-ligand complex F is the most likely binding hypothesis for the studied benzoxazine analogs.

AB - Molecular docking and 3D-QSAR studies were performed to determine the binding mode for a series of benzoxazine oxytocin antagonists taken from the literature. Structural hypotheses were generated by docking the most active molecule to the rigid receptor by means of AutoDock 3.05. The cluster analysis yielded seven possible binding conformations. These structures were refined by using constrained simulated annealing, and the further ligands were aligned in the refined receptor by molecular docking. A good correlation was found between the estimated Delta;Gbind and the pKi values for complex F. The Connolly-surface analysis, CoMFA and CoMSIA models qCoMFA 2 = 0.653, qCoMSA2 = 0.630 and rpred,CoMFA2 = 0.852, rpred,CoMSIA 2 = 0.815) confirmed the scoring function results. The structural features of the receptor-ligand complex and the CoMFA and CoMSIA fields are in closely connected. These results suggest that receptor-ligand complex F is the most likely binding hypothesis for the studied benzoxazine analogs.

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KW - Scoring function

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