Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
권호 표지
DOI QR코드

DOI QR Code

Homology Modeling of GPR18 Receptor, an Orphan G-protein-coupled Receptor

  • Kothandan, Gugan (Department of Biochemistry, Centre for Bioinformatics, University of Madras, Guindy Campus) ;
  • Cho, Seung Joo (Department of Bio-New Drug Development College of Medicine, Chosun University)
  • Received : 2013.02.18
  • Accepted : 2013.03.25
  • Published : 2013.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

G-protein-coupled receptor (GPCR) superfamily is the largest known receptor family, characterized by seven transmembrane domains and considered to be an important drug target. In this study we focused on an orphan GPCR termed as GPR18. As there is no X-ray crystal structure has been reported for this receptor, we report on a homology model of GPR18. Template structure with high homology was used for modeling and ten models were developed. A model was selected and refined by energy minimization. The selected model was further validated using various parameters. Our results could be a starting point for further structure based drug design.

Keywords

References

  1. M. D. Thompson, W. M. Burnham, and D. E. Cole, "The G protein-coupled receptors: pharmacogenetics and disease", Crit. Rev. Clin. Lab. Sci., Vol. 42, pp. 311-392, 2005. https://doi.org/10.1080/10408360591001895
  2. R. J. Lefkowitz, "Historical review: a brief history and personal retrospective of seven-transmembrane receptors", Trends Pharmacol., Sci., Vol. 25, pp. 413-422, 2004. https://doi.org/10.1016/j.tips.2004.06.006
  3. S. Schlyer and R. Horuk, "I want a new drug: Gprotein-coupled receptors", Drug Discov. Today, Vol. 11, pp. 481-493, 2006. https://doi.org/10.1016/j.drudis.2006.04.008
  4. M. Kohno, H. Hasegawa, A. Inoue, M. Muraoka, T. Miyazaki, K. Oka, and M. Yasukawa, "Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR18", Biochem. Biophys. Res. Commun., Vol. 347, pp. 827-832, 2006. https://doi.org/10.1016/j.bbrc.2006.06.175
  5. G. Kothandan, T. Madhavan, C. G. Gadhe, and S. J. Cho, "Pseudoreceptor: Concept and an overview", J. Chosun Natural Sci., Vol. 5, pp. 216-219, 2012. https://doi.org/10.13160/ricns.2012.5.4.216
  6. G. Kothandan and S. J. Cho, "Prediction of binding free energy calculation using molecular mechanics/ Poisson-Boltzmann surface area (MM-PBSA) method in drug discovery: A short review", J. Chosun Natural Sci., Vol. 2, pp. 55-58, 2009.
  7. S. J. Cho, "Search space reduction techniques in small molecular docking", J. Chosun Natural Sci. Vol. 3, pp. 143-147, 2010.
  8. S. J. Cho, "Calculation and application of partial charges", J. Chosun Natural Sci., Vol. 3, pp. 226-230, 2010.
  9. S. J. Cho, "Meaning and definition of partial charges", J. Chosun Natural Sci., Vol. 3, pp. 231-236, 2010.
  10. S. F. Altschul, W. Gish, W. Miller, E. W. Myers, and D. J. Lipman, "Basic local alignment search tool", J. Mol. Biol., Vol. 215, pp 403-410, 1990. https://doi.org/10.1016/S0022-2836(05)80360-2
  11. S. F. Altschul, T. L. Madden, A. A. Schaffer, J. Zhang, Z. Zhang, W. Miller, and D. J. Lipman, "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs", Nucleic Acids Res., Vol. 50, pp. 3389-3402, 1997.
  12. H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, and P. E. Bourne, "The protein data bank", Nucleic Acids Res., Vol. 28, pp. 235-242, 2000. https://doi.org/10.1093/nar/28.1.235
  13. J. D. Thompson, D. G. Higgins, and T. J. Gibson, "CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice", Nucleic Acids Res., Vol. 22, pp. 4673-4680, 1994. https://doi.org/10.1093/nar/22.22.4673
  14. N. Eswar, B. John, N. Mirkovic, A. Fiser, V. A. Ilyin, U. Pieper, A. C. Stuart, M. A. Marti-Renom, M. S. Madhusudhan, B. Yerkovich, and A. Sali, "Tools for comparative protein structure modeling and analysis", Nucleic Acids Res., Vol. 31, pp. 3375-3380, 2003. https://doi.org/10.1093/nar/gkg543
  15. A. Sali and T. L. Blundell, "Comparative protein modeling by satisfaction of spatial restraints", J. Mol. Biol., Vol. 234, pp. 779-815, 1993. https://doi.org/10.1006/jmbi.1993.1626
  16. A. Fiser, R. K. Do, and A. Sali, "Modeling of loops in protein structures", Protein Sci., Vol. 9, pp. 1753-1773, 2002.
  17. R. A. Laskowski, M. W. MacArthur, D. S. Moss, and J. M. Thornton, "Procheck-a program to check the stereochemical quality of protein structures", J. Appl. Cryst., Vol. 26, pp. 283-291, 1993. https://doi.org/10.1107/S0021889892009944
  18. C. Colovos and T.O. Yeates, "Verification of protein structures: patterns of nonbonded atomic interactions", Protein Sci., Vol. 2, pp. 1511-1519, 1993. https://doi.org/10.1002/pro.5560020916
  19. A. A. Thompson, W. Liu, E. Chun, V. Katritch, H. Wu, E. Vardy, X. P. Huang, C. Trapella, R. Guerrini, G. Clo, B. L. Roth, V. Cherezov, and R. C. Stevens, "Structure of the nociceptin/orphanin FQ receptor in complex with a pepti de mimetic", Nature, Vol. 485, pp. 395-399, 2012. https://doi.org/10.1038/nature11085
  20. Y. Qin, E. M. E. Verdegaal, M. Siderius, J. P. Bebelman, M. J. Smit, R. Leurs, R. Willemze, C. P. Tensen, and S. Osanto, "Quantitative expression proling of G-protein-coupled receptors (GPCRs) in metastatic melanoma: the constitutively active orphan GPCR GPR18 as novel drug target", Pig. Cell Melanoma R., Vol. 24, pp. 207-218, 2010.

Cited by

  1. Theoretical analysis of somatostatin receptor 5 with antagonists and agonists for the treatment of neuroendocrine tumors vol.21, pp.2, 2017, https://doi.org/10.1007/s11030-016-9722-7
  2. Isolation, purification and characterization of proteinaceous fungal α-amylase inhibitor from rhizome of Cheilocostus speciosus (J.Koenig) C.D.Specht vol.111, 2018, https://doi.org/10.1016/j.ijbiomac.2017.12.158
  3. Structural characterization of human CRTh2: a combined homology modeling, molecular docking and 3D-QSAR-based in silico approach vol.25, pp.4, 2016, https://doi.org/10.1007/s00044-016-1516-z
  4. G protein coupled receptor 18: A potential role for endocannabinoid signaling in metabolic dysfunction vol.60, pp.1, 2016, https://doi.org/10.1002/mnfr.201500449
  5. Toward a better understanding of the interaction between somatostatin receptor 2 and its ligands: a structural characterization study using molecular dynamics and conceptual density functional theory pp.1538-0254, 2018, https://doi.org/10.1080/07391102.2018.1508368
  6. Advancements in therapeutically targeting orphan GPCRs vol.6, pp.None, 2013, https://doi.org/10.3389/fphar.2015.00100
  7. Molecular Modeling of an Orphan GPR18 Receptor vol.15, pp.None, 2013, https://doi.org/10.2174/1570180815666180810114847
  8. Computational Investigations on the Binding Mode of Ligands for the Cannabinoid-Activated G Protein-Coupled Receptor GPR18 vol.10, pp.5, 2013, https://doi.org/10.3390/biom10050686