Skip to main content
SpringerLink
Log in

Angiotensin II Type 1 Receptor Homology Models: A Comparison Between In Silico and the Crystal Structures

  • Protocol
  • First Online:
Book cover Rational Drug Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1824))

Abstract

For many years structural studies of the angiotensin II type 1 receptor (AT1R) solely relied on mutagenesis experiments combined with homology modeling. The recent publication of the co-crystallized structures of AT1R with the antagonists ZD7155 and olmesartan allows comparative studies. In this chapter the binding modes of olmesartan in the crystal structures and the homology models are compared utilizing mutagenesis data. The obtained results suggest that both homology and crystal structures should be used for future rational drug design. Of paramount importance are these co-crystallized structures or homology models to be simulated in a lipid bilayer environment that mimics the biological.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Zhang H, Unal H, Gati C et al (2015) Structure of the angiotensin receptor revealed by serial femtosecond crystallography. Cell 161(4):833–844. https://doi.org/10.1016/j.cell.2015.04.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhang H, Unal H, Desnoyer R et al (2015) Structural basis for ligand recognition and functional selectivity at angiotensin receptor. J Biol Chem 290(49):29127–29139. https://doi.org/10.1074/jbc.M115.689000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rataj K, Witek J, Mordalski S et al (2014) Impact of template choice on homology model efficiency in virtual screening. J Chem Inf Model 54(6):1661–1668. https://doi.org/10.1021/ci500001f

    Article  CAS  PubMed  Google Scholar 

  4. Xiang J, Chun E, Liu C et al (2016) Successful strategies to determine high-resolution structures of GPCRs. Trends Pharmacol Sci 37(12):1055–1069. https://doi.org/10.1016/j.tips.2016.09.009

    Article  CAS  PubMed  Google Scholar 

  5. Kellici TF, Ntountaniotis D, Kritsi E et al (2016) Leveraging NMR and X-ray data of the free ligands to build better drugs targeting angiotensin II type 1 G-protein coupled receptor. Curr Med Chem 23(1):36–59. https://doi.org/10.2174/0929867323666151117122116

    Article  CAS  PubMed  Google Scholar 

  6. Kellici TF, Tzakos AG, Mavromoustakos T (2015) Rational drug design and synthesis of molecules targeting the angiotensin II type 1 and type 2 receptors. Molecules 20(3):3868–3897. https://doi.org/10.3390/molecules20033868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Miura SI, Fujino M, Hanzawa H et al (2006) Molecular mechanism underlying inverse agonist of angiotensin II type 1 receptor. J Biol Chem 281(28):19288–19295. https://doi.org/10.1074/jbc.M602144200

    Article  CAS  PubMed  Google Scholar 

  8. Miura S, Nakao N, Hanzawa H et al (2013) Reassessment of the unique mode of binding between angiotensin II type 1 receptor and their blockers. PLoS One 8(11):e79914. https://doi.org/10.1371/journal.pone.0079914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Miura S, Kiya Y, Hanzawa H et al (2012) Small molecules with similar structures exhibit agonist, neutral antagonist or inverse agonist activity toward angiotensin II type 1 receptor. PLoS One 7(6):e37974. https://doi.org/10.1371/journal.pone.0037974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kellici TF, Ntountaniotis D, Liapakis G et al (2016) The dynamic properties of angiotensin II type 1 receptor inverse agonists in solution and in the receptor site. Arab J Chem. https://doi.org/10.1016/j.arabjc.2016.11.014

  11. Madhavi Sastry G, Adzhigirey M, Day T et al (2013) Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des 27(3):221–234. https://doi.org/10.1007/s10822-013-9644-8

    Article  CAS  PubMed  Google Scholar 

  12. Small-Molecule Drug Discovery Suite 2015–2 (2015) Schrödinger Suite 2015-2 QM-Polarized Ligand Docking protocol; Glide version 6.7, Schrödinger, LLC, New York, NY, 2015; Jaguar version 8.8, Schrödinger, LLC, New York, NY, 2015; QSite version 6.7, Schrödinger, LLC, New York, NY

    Google Scholar 

  13. Small-Molecule Drug Discovery Suite 2015–2 (2015) Schrödinger Suite 2015-2 Induced Fit Docking protocol; Glide version 6.7, Schrödinger, LLC, New York, NY, 2015; Prime version 4.0, Schrödinger, LLC, New York, NY

    Google Scholar 

  14. Jacobson MP, Pincus DL, Rapp CS et al (2004) A hierarchical approach to all-atom protein loop prediction. Proteins 55(2):351–367. https://doi.org/10.1002/prot.10613

    Article  CAS  PubMed  Google Scholar 

  15. Schrödinger Release 2015–2 (2015) Desmond Molecular Dynamics System, version 4.2, D. E. Shaw Research, New York, NY, 2015. Maestro-Desmond Interoperability Tools, version 4.2, Schrödinger, New York, NY

    Google Scholar 

  16. Yanagisawa H, Amemiya Y, Kanazaki T et al (1996) Nonpeptide angiotensin II receptor antagonists: synthesis, biological activities, and structure - activity relationships of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds. J Med Chem 39(1):323–338

    Article  CAS  PubMed  Google Scholar 

  17. Tuccinardi T, Calderone V, Rapposelli S et al (2006) Proposal of a new binding orientation for non-peptide AT1 antagonists: homology modeling, docking and three-dimensional quantitative structure-activity relationship analysis. J Med Chem 49(14):4305–4316. https://doi.org/10.1021/jm060338p

    Article  CAS  PubMed  Google Scholar 

  18. Matsoukas MT, Cordomi A, Rios S et al (2013) Ligand binding determinants for angiotensin II type 1 receptor from computer simulations. J Chem Inf Model 53(11):2874–2883. https://doi.org/10.1021/ci400400m

    Article  CAS  PubMed  Google Scholar 

  19. Matsoukas MT, Potamitis C, Plotas P et al (2013) Insights into AT1 receptor activation through AngII binding studies. J Chem Inf Model 53(11):2798–2811. https://doi.org/10.1021/ci4003014

    Article  CAS  PubMed  Google Scholar 

  20. Olsson MHM, Søndergaard CR, Rostkowski M et al (2011) PROPKA3: consistent treatment of internal and surface residues in empirical p K a predictions. J Chem Theory Comput 7(2):525–537. https://doi.org/10.1021/ct100578z

    Article  CAS  PubMed  Google Scholar 

  21. Harder E, Damm W, Maple J et al (2016) OPLS3: a force field providing broad coverage of drug-like small molecules and proteins. J Chem Theory Comput 12(1):281–296. https://doi.org/10.1021/acs.jctc.5b00864

    Article  CAS  PubMed  Google Scholar 

  22. Zhu K, Day T, Warshaviak D et al (2014) Antibody structure determination using a combination of homology modeling, energy-based refinement, and loop prediction. Proteins 82(8):1646–1655. https://doi.org/10.1002/prot.24551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Small-Molecule Drug Discovery Suite 2015–2 (2015) Glide, version 6.7, Schrödinger, LLC, New York, NY

    Google Scholar 

  24. Friesner RA, Murphy RB, Repasky MP et al (2006) Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 49(21):6177–6196. https://doi.org/10.1021/jm051256o

    Article  CAS  PubMed  Google Scholar 

  25. Sherman W, Day T, Jacobson MP et al (2006) Novel procedure for modeling ligand/receptor induced fit effects. J Med Chem 49(2):534–553. https://doi.org/10.1021/jm050540c

    Article  CAS  PubMed  Google Scholar 

  26. Tuckerman M, Berne BJ, Martyna GJ (1992) Reversible multiple time scale molecular dynamics. J Chem Phys 97(3):1990–2001

    Article  CAS  Google Scholar 

  27. Martyna GJ, Klein ML, Tuckerman M (1992) Nosé-hoover chains: the canonical ensemble via continuous dynamics. J Chem Phys 97(4):2635–2643

    Article  Google Scholar 

  28. Martyna GJ, Tobias DJ, Klein ML (1994) Constant pressure molecular dynamics algorithms. J Chem Phys 101(5):4177–4189

    Article  CAS  Google Scholar 

  29. Netticadan TJ, Ashavaid TF, Nair KG (1997) Characterisation of the canine cardiac sarcolemma in experimental myocardial ischemia. Indian J Clin Biochem 12(1):49–54. https://doi.org/10.1007/bf02867955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Oliveira TR, Lamy MT, De Paula UM et al (2009) Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes. Braz J Med Biol Res 42(9):844–853

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

T.K. is extremely grateful to Prof. Thomas Mavromoustakos for his supporting and funding.

Author information

Authors and Affiliations

  1. Division of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, Athens, Greece

    Tahsin F. Kellici

Authors
  1. Tahsin F. Kellici
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, Athens, Greece

    Thomas Mavromoustakos

  2. Division of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, Athens, Greece

    Tahsin F. Kellici

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Kellici, T.F. (2018). Angiotensin II Type 1 Receptor Homology Models: A Comparison Between In Silico and the Crystal Structures. In: Mavromoustakos, T., Kellici, T. (eds) Rational Drug Design. Methods in Molecular Biology, vol 1824. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8630-9_27

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8630-9_27

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8629-3

  • Online ISBN: 978-1-4939-8630-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation