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Molecular Modelling of Odorant/Olfactory Receptor Complexes

  • Landry Charlier
  • Jérémie Topin
  • Claire A. de March
  • Peter C. Lai
  • Chiquito J. Crasto
  • Jerome Golebiowski
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1003)

Abstract

Providing a rationale that associates a chemical structure of an odorant to its induced perception has been sought for a long time. To achieve this, a detailed atomic structure of both the odorant and the olfactory receptor must be known. State-of-the-art techniques to model the 3D structure of an olfactory receptor in complex with various odorants are presented here. These range from sequence alignment with known structures to molecular dynamics simulations in a realistic environment.

Key words

Molecular modelling Homology 3D-structure Docking GPCR Olfactory receptor MM-GBSA 

Notes

Acknowledgments

The CINES is acknowledged for providing computer time for the project cmi1024.

References

  1. 1.
    Breer H (1994) Odor recognition and second messenger signalling in olfactory receptor neurons. Semin Cell Dev Biol 5:25–32CrossRefGoogle Scholar
  2. 2.
    Malnic B, Hirono J, Sato T, Buck L (1999) Combinatorial receptor codes for odorants. Cell 96:713–723PubMedCrossRefGoogle Scholar
  3. 3.
    Rossiter KJ (1996) Structure-odor relationships. Chem Rev 96:3201–3240PubMedCrossRefGoogle Scholar
  4. 4.
    Cozzetto D, Tramontano A (2008) Advances and pitfalls in protein structure prediction. Curr Protein Pept Sci 9:567–577PubMedCrossRefGoogle Scholar
  5. 5.
    Abrol R, Bray JK, Goddard WA III (2011) BiHelix: towards de novo structure prediction of an ensemble of G-protein coupled receptor conformations. Proteins 80:505–518CrossRefGoogle Scholar
  6. 6.
    Charlier L, Topin J, Ronin C, Kim SK, Goddard WA III, Efremov R, Golebiowski J (2012) How broadly tuned olfactory receptors equally recognize their agonists. Human OR1G1 as a test case. Cell Mol Life Sci 69:4205–4213. doi: 10.1007/s00018-012-1116-0 PubMedCrossRefGoogle Scholar
  7. 7.
    Okada T, Sugihara M, Bondar A-N, Elstner M, Entel P, Buss V (2004) The retinal conformation and its environment in rhodopsin in light of a new 2.2.ANG. crystal structure. J Mol Biol 342(2):571–583PubMedCrossRefGoogle Scholar
  8. 8.
    Jaakola V-P, Griffith MT, Hanson MA, Cherezov V, Chien EYT, Lane JR, Ijzerman AP, Stevens RC (2008) The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 322(5905):1211–1217PubMedCrossRefGoogle Scholar
  9. 9.
    Warne T, Serrano-Vega MJ, Baker JG, Moukhametzianov R, Edwards PC, Henderson R, Leslie AGW, Tate CG, Schertler GFX (2008) Structure of a beta 1-adrenergic G-protein-coupled receptor. Nature 454(7203):486–491PubMedCrossRefGoogle Scholar
  10. 10.
    Cherezov V, Rosenbaum Daniel M, Hanson Michael A, Rasmussen Soren GF, Thian Foon S, Kobilka Tong S, Choi H-J, Kuhn P, Weis William I, Kobilka Brian K, Stevens Raymond C (2007) High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318(5854):1258–1265PubMedCrossRefGoogle Scholar
  11. 11.
    Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V, Abagyan R, Brooun A, Wells P, Bi FC, Hamel DJ, Kuhn P, Handel TM, Cherezov V, Stevens RC (2010) Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330(6007):1066–1071PubMedCrossRefGoogle Scholar
  12. 12.
    Chien EY, Liu W, Zhao Q, Katritch V, Han GW, Hanson MA, Shi L, Newman AH, Javitch JA, Cherezov V, Stevens RC (2010) Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 330(6007):1091–1095PubMedCrossRefGoogle Scholar
  13. 13.
    Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S (2011) Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Nature 475(7354):65–70PubMedCrossRefGoogle Scholar
  14. 14.
    Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, Reinhart G, Desale H, Clemons B, Cahalan SM, Schuerer SC, Sanna MG, Han GW, Kuhn P, Rosen H, Stevens RC (2012) Crystal structure of a lipid G protein-coupled receptor. Science 335(6070):851–855PubMedCrossRefGoogle Scholar
  15. 15.
    Zozulya S, Echeverri F, Nguyen T (2001) The human olfactory receptor repertoire. Genome Biol 2(6):18CrossRefGoogle Scholar
  16. 16.
    Man O, Gilad Y, Lancet D (2004) Prediction of the odorant binding site of olfactory receptor proteins by human-mouse comparisons. Protein Sci 13(1):240–254PubMedCrossRefGoogle Scholar
  17. 17.
    Schmiedeberg K, Shirokova E, Weber H-P, Schilling B, Meyerhof W, Krautwurst D (2007) Structural determinants of odorant recognition by the human olfactory receptors OR1A1 and OR1A2. J Struct Biol 159(3):400–412PubMedCrossRefGoogle Scholar
  18. 18.
    Doszczak L, Kraft P, Weber H-P, Bertermann R, Triller A, Hatt H, Tacke R (2007) Prediction of perception: probing the hOR17-4 olfactory receptor model with silicon analogues of bourgeonal and lilial. Angew Chem Int Ed 46(18):3367–3371CrossRefGoogle Scholar
  19. 19.
    Hall SE, Floriano WB, Vaidehi N, Goddard WA III (2004) Predicted 3-D structures for mouse I7 and rat I7 olfactory receptors and comparison of predicted odor recognition profiles with experiment. Chem Senses 29(7):595–616PubMedCrossRefGoogle Scholar
  20. 20.
    Abaffy T, Malhotra A, Luetje CW (2007) The molecular basis for ligand specificity in a mouse olfactory receptor: a network of functionally important residues. J Biol Chem 282(2):1216–1224PubMedCrossRefGoogle Scholar
  21. 21.
    Hummel P, Vaidehi N, Floriano WB, Hall SE, Goddard WA III (2005) Test of the binding threshold hypothesis for olfactory receptors: explanation of the differential binding of ketones to the mouse and human orthologs of olfactory receptor 912-93. Protein Sci 14(3):703–710PubMedCrossRefGoogle Scholar
  22. 22.
    Floriano WB, Vaidehi N, Goddard WA III, Singer MS, Shepherd GM (2000) Molecular mechanisms underlying differential odor responses of a mouse olfactory receptor. Proc Natl Acad Sci U S A 97(20):10712–10716PubMedCrossRefGoogle Scholar
  23. 23.
    Singer MS (2000) Analysis of the molecular basis for octanal interactions in the expressed rat 17 olfactory receptor. Chem Senses 25(2):155–165PubMedCrossRefGoogle Scholar
  24. 24.
    Baud O, Etter S, Spreafico M, Bordoli L, Schwede T, Vogel H, Pick H (2011) The mouse eugenol odorant receptor: structural and functional plasticity of a broadly tuned odorant binding pocket. Biochemistry 50(5):843–853PubMedCrossRefGoogle Scholar
  25. 25.
    Gelis L, Wolf S, Hatt H, Neuhaus EM, Gerwert K (2012) Prediction of a ligand-binding niche within a human olfactory receptor by combining site-directed mutagenesis with dynamic homology modeling. Angew Chem Int Ed 51:1274–1278CrossRefGoogle Scholar
  26. 26.
    Avlani VA, Gregory KJ, Morton CJ, Parker MW, Sexton PM, Christopoulos A (2007) Critical role for the second extracellular loop in the binding of both orthosteric and allosteric G protein-coupled receptor ligands. J Biol Chem 282:25677–25686PubMedCrossRefGoogle Scholar
  27. 27.
    Nagle JF, Tristram-Nagle S (2000) Structure of lipid bilayers. Biochim Biophys Acta 1469(3):159–195PubMedCrossRefGoogle Scholar
  28. 28.
    Kandt C, Ash WL, Tieleman DP (2007) Setting up and running molecular dynamics simulations of membrane proteins. Methods 41(4):475–488PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Landry Charlier
    • 1
  • Jérémie Topin
    • 1
  • Claire A. de March
    • 1
  • Peter C. Lai
    • 2
  • Chiquito J. Crasto
    • 2
  • Jerome Golebiowski
    • 1
  1. 1.Institut de Chimie de Nice, UMR CNRSUniversité de Nice Sophia AntipolisNiceFrance
  2. 2.Division of Research, Department of GeneticsUniversity of Alabama at BirminghamBirminghamUSA

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