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Possible dynamic anchor points in a benzoxazinone derivative–human oxytocin receptor system — a molecular docking and dynamics calculation

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Abstract

In this study, we performed a molecular docking and dynamics simulation for a benzoxazinone–human oxytocin receptor system to determine the possible hydrophobic and electrostatic interaction points in the dynamic complex. After the homology modeling, the ligand was docked into the putative active using AutoDock 3.05. After the application of energetic and structural filters, the complexes obtained were further refined with a simulated annealing protocol (AMBER8) to remove steric clashes. Three complexes were selected for subjection to the molecular dynamics simulation (5 ns), and the results on the occurrence of average anchor points showed a stable complex between the benzoxazinone derivative and the receptor. The complex could be used as a good starting point for further analysis with site-directed mutagenesis, or further computational research.

The location of the ligands (complex B – blue; complex E – red; and complex F – green) in the transmembrane regions (TM1 – red; TM2 – blue; TM3 – yellow; TM4 – purple; TM5 – orange; TM6 – cyan; TM7 – pink) of the hOTR. For clarity, the EC and IC loops are not shown

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Abbreviations

OTR:

Oxytocin receptor

OT:

Oxytocin

hOTR:

Human oxytocin receptor

MD:

Molecular dynamics

BZX:

Benzoxazinone

GPCRs:

G-protein coupled receptors

TM:

Transmembrane

SA:

Simulated annealing

bRho:

Bovine rhodopsin

RMSD:

Root-mean-square distance

GAFF:

General Amber Force Field

ΔG bind :

Estimated free energy of binding

EC:

Extracellular

IC:

Intracellular

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Acknowledgements

This work was supported by the Centenarium Foundation of Gedeon Richter and the National Council for Research and Technology (NKFP) Budapest (RET 08/2004).

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Authors and Affiliations

  1. Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, 6721, Szeged, Hungary

    Balázs Jójárt & Árpád Márki

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  1. Balázs Jójárt
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  2. Árpád Márki
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Correspondence to Balázs Jójárt.

Additional information

Supplementary Material

The 3D-coordinates of complex B, E and F in pdb format are available as supplementary material, together with the parameter topology file of BZX.

Electronic supplementary material

These files are unfortunately not in the Publisher's archive anymore:

  • Supplement 1 (PDB 44 kb)

  • Supplement 2 (PDB 291 kb)

  • Supplement 3 (PDB 291 kb)

  • Supplement 4 (PDB 291 kb)

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Jójárt, B., Márki, Á. Possible dynamic anchor points in a benzoxazinone derivative–human oxytocin receptor system — a molecular docking and dynamics calculation. J Mol Model 13, 1–10 (2007). https://doi.org/10.1007/s00894-006-0112-4

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  • DOI: https://doi.org/10.1007/s00894-006-0112-4

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