Journal of Central South University

, Volume 19, Issue 11, pp 3033–3039 | Cite as

Multiple templates-based homology modeling and docking analysis of angiotensin II type 1 receptor

  • Yun-feng Xie (谢云丰)
  • Yu-ren Jiang (蒋玉仁)
  • Ya-fei Pan (潘亚飞)
  • Dan Chen (陈丹)
  • Chuan-jun Li (李传俊)
Article
First Online:
Received:
Accepted:

Abstract

Using the latest reported homologous Chemokine receptors (PDB ID: 3ODU, 3OE0 and 3OE6) as templates, twenty models of angiotensin II (Ang II) type 1 (AT1) receptor (known as p30556) were generated by multiple templates homology modeling. According to the results of the initial validation of these twenty models, the model 0020 was finally chosen as the best one for further studies. Then, a 2 ns molecular dynamic (MD) simulation for model 0020 was conducted in normal saline (0.9%, w/V) under periodical boundary conditions, which was followed by docking studies of model 0020 with several existing AT1 receptor blockers (ARBs). The docking results reveal that model 0020 possesses good affinities with these docked ARBs which are in accordance with both the IC50 inhibitor values and their curative effects. The results also show more potent interactions between the model 0020 and its ARBs than those of ever reported results, such as hydrogen bonds, hydrophobic interactions, and especially cation-π interactions and π-π interactions which have never been reported before. This may reveal that the structure of the model 0020 is quite close to its real crystal structure and the model 0020 may have the potential to be used for structure based drug design.

Key words

angiotensin II type 1 receptor docking homology modeling molecular dynamics 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    LAZICH I, BAKRIS G L. Newer renin-angiotensin-aldosterone system blocker combinations: Is there an advantage? [J]. Curr Opin Nephrol Hypertens, 2011, 20(5): 471–475.CrossRefGoogle Scholar
  2. [2]
    VYAS V K, GHATE M. Substituted benzimidazole derivatives as angiotensin II-AT1 receptor antagonist: A review [J]. Mini Rev Med Chem, 2010, 10(14): 1366–1384.CrossRefGoogle Scholar
  3. [3]
    ISMAIL M A, BARKER S, ABOU EL-ELLA DA, ABOUZID K A, TOUBAR R A, TODD M H. Design and synthesis of new tetrazolyl- and carboxy-biphenylylmethyl-quinazolin-4-one derivatives as angiotensin II AT1 receptor antagonists [J]. J Med Chem, 2006, 49(5): 1526–1535.CrossRefGoogle Scholar
  4. [4]
    CAPPELLI A, PERICOT MOHR GL G, GALLELLI A, RIZZO M, ANZINI M, VOMERO S. Design, synthesis, structural studies, biological evaluation, and computational simulations of novel potent AT(1) angiotensin II receptor antagonists based on the 4-phenylquinoline structure [J]. J Med Chem, 2004, 47(10): 2574–2586.CrossRefGoogle Scholar
  5. [5]
    GOLDFELD D A, ZHU Kai, BEUMING T, FRIESNER R A. Successful prediction of the intra- and extracellular loops of four G-protein-coupled receptors [J]. Proc Natl Acad Sci USA, 2011, 108(20): 8275–8280.CrossRefGoogle Scholar
  6. [6]
    VILAR S, FERINO G, PHATAK S S, BERK B, CAVASOTTO C N, COSTANZI S. Docking-based virtual screening for ligands of G protein-coupled receptors: Not only crystal structures but also in silico models [J]. J Mol Graph Model, 2011, 29(5): 614–623.CrossRefGoogle Scholar
  7. [7]
    TAPANEEYAKOM S, GODDARD A D, OATES J, WILLIS C L, WATTS A. Solution- and solid-state NMR studies of GPCRs and their ligands [J]. Biochim Biophys Acta, 2011, 1808(6): 1462–1475.CrossRefGoogle Scholar
  8. [8]
    MUGUMBATE G, JACKSON G E, van der SPOEL D. Open conformation of adipokinetic hormone receptor from the malaria mosquito facilitates hormone binding [J]. Peptides, 2011, 32(3): 553–559.CrossRefGoogle Scholar
  9. [9]
    KATRITCH V, RUEDA M, LAM P C, YEAGER M, ABAGYAN R. GPCR 3D homology models for ligand screening: Lessons learned from blind predictions of adenosine A2a receptor complex [J]. Proteins, 2010, 78(1): 197–211.CrossRefGoogle Scholar
  10. [10]
    LI Y Y, HOU T J, GODDARD III W A. Computational modeling of structure-function of g protein-coupled receptors with applications for drug design [J]. Curr Med Chem, 2010, 17(12): 1167–1180.CrossRefGoogle Scholar
  11. [11]
    YEAGLE P L, ALBERT A D. G-protein coupled receptor structure [J]. Biochim Biophys Acta, 2007, 1768(4): 808–824.CrossRefGoogle Scholar
  12. [12]
    CAVASOTTO C N, PHATAK S S. Homology modeling in drug discovery: Current trends and applications [J]. Drug Discov Today, 2009, 14(13/14): 676–683.CrossRefGoogle Scholar
  13. [13]
    SOKKAR P, MOHANDASS S, RAMACHANDRAN M. Multiple templates-based homology modeling enhances structure quality of AT1 receptor: Validation by molecular dynamics and antagonist docking [J]. J Mol Model, 2011, 17(7): 1565–1577.CrossRefGoogle Scholar
  14. [14]
    PATNY A, DESAI P V, AVERY M A. Ligand-supported homology modeling of the human angiotensin II type 1 (AT(1)) receptor: Insights into the molecular determinants of telmisartan binding [J]. Proteins, 2006, 65(4): 824–842.CrossRefGoogle Scholar
  15. [15]
    YAMITZKY T, LEVIT A, NIV M Y. Homology modeling of G-protein-coupled receptors with X-ray structures on the rise [J]. Curr Opin Drug Discov Devel, 2010, 13(3): 317–325.Google Scholar
  16. [16]
    WU Bei-li, CHIEN E Y, MOL C D, FENALTI G, LIU Wei, KATRITCH V, ABAGYAN R, BROOUN A, WELLS P, BI F C, HAMEL D J, KUHN P, HANDEL T M, CHEREZOV V, STEVENS R C. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists [J]. Science, 2010, 330(6007): 1066–1071.CrossRefGoogle Scholar
  17. [17]
    FLOWER D R. Modelling G-protein-coupled receptors for drug design [J]. Biochim Biophys Acta, 1999, 1422(3): 207–234.CrossRefGoogle Scholar
  18. [18]
    NIKIFOROVICH G V, MARSHALL G R. 3D model for TM region of the AT-1 receptor in complex with angiotensin II independently validated by site-directed mutagenesis data [J]. Biochem Biophys Res Commun, 2001, 286(5): 1204–1211.CrossRefGoogle Scholar
  19. [19]
    GUEX N, PEITSCH M C. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling [J]. Electrophoresis, 1997, 18(15): 2714–2723.CrossRefGoogle Scholar
  20. [20]
    SALI A, BLUNDELL T L. Comparative protein modelling by satisfaction of spatial restraints [J]. J Mol Biol, 1993, 234(3): 779–815.CrossRefGoogle Scholar
  21. [21]
    LINDORFF-LARSEN K, PIANA S, PALMO K, MARAGAKIS P, KLEOEIS J L, DROR R O, SHAW D E. Improved side-chain torsion potentials for the Amber ff99SB protein force field [J]. Proteins, 2010, 78(8): 1950–1958.Google Scholar
  22. [22]
    HESS B, KUTZNER C, van der SPOEL D, LINDAHL E. GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation [J]. Journal of Chemical Theory and Computation, 2008, 4(3): 435–447.CrossRefGoogle Scholar
  23. [23]
    BUSSI G, DONADIO D, PARRINELLO M. Canonical sampling through velocity rescaling [J]. J Chem Phys, 2007, 126(1): 014101.CrossRefGoogle Scholar
  24. [24]
    MIYAMOTO S, KOLLMAN P A. SETTLE: An analytical version of the SHAKE and RATTLE algorithms for rigid water models [J]. J Comp Chem, 1992, 13(8): 952–962.CrossRefGoogle Scholar
  25. [25]
    HESS B, BEKKER H, BERENDSEN H J C, FRAAIJE J G E M. LINCS: A linear constraint solver for molecular simulations [J]. J Comb Chem, 1997, 18(12): 1463–1472.CrossRefGoogle Scholar
  26. [26]
    ESSMAN U, PERELA L, BERKOWITZ ML, DARDEN T, LEE H, PEDERSEN L G. A smooth particle mesh Ewald method [J]. J Chem Phys, 1995, 103(19): 8577–8592.CrossRefGoogle Scholar
  27. [27]
    JONES G, WILLETT P, GLEN R C, LEACH A R, TAYLOR R. Development and validation of a genetic algorithm for flexible docking [J]. J Mol Biol, 1997, 267(3): 727–748.CrossRefGoogle Scholar
  28. [28]
    OHNO K, AMANO Y, KAKUTA H, NIIMI T, TAKAKURA S, ORITA M, MIYATA K, SAKASHITA H, TAKEUCHI M, KOMURO I, HIGAKI J, HORIUCHI M, KIM-MITSUYAMA S, MORI Y, MORISHITA R, YAMAGISHI S. Unique “delta lock” structure of telmisartan is involved in its strongest binding affinity to angiotensin II type 1 receptor [J]. Biochem Biophys Res Commun, 2011, 404(1): 434–437.CrossRefGoogle Scholar

Copyright information

© Central South University Press and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Yun-feng Xie (谢云丰)
    • 1
  • Yu-ren Jiang (蒋玉仁)
    • 1
  • Ya-fei Pan (潘亚飞)
    • 1
  • Dan Chen (陈丹)
    • 1
  • Chuan-jun Li (李传俊)
    • 1
  1. 1.College of Chemistry and Chemical EngineeringCentral South UniversityChangshaChina

Personalised recommendations