SpringerLink
Log in

Constant pH molecular dynamics (CpHMD) and molecular docking studies of CquiOBP1 pH-induced ligand releasing mechanism

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

The odorant binding protein of Culex quinquefasciatus (CquiOBP1), expressed on the insect antenna, is crucial for the investigation of trap** baited with oviposition semi-chemicals and controlling mosquito populations. The acidic titratable residues pKa prediction and the ligand binding poses investigation in two systems (pH 7 and pH 5) are studied by constant pH molecular dynamics (CpHMD) and molecular docking methods. Research results reveal that the change of the protonation states would disrupt some important H-bonds, such as Asp 66-Asp 70, Glu 105-Asn 102, etc. The cleavage of these H-bonds leads to the movement of the relative position of hydrophobic tunnel, N- and C- termini loops and pH-sensing triad (His23-Tyr54-Val125) in acid solution. Ligand MOP has lower affinity and shows different binding poses to protein CquiOBP1 at pH 5. This ligand may be released from another tunnel between helices α3 and α4 in acidic environment. However, it would bind to the protein with high affinity in neutral environment. This work could provide more penetrating understanding of the pH-induced ligand-releasing mechanism.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Benton R (2006) On the origin of smell: odorant receptors in insects. Cell Mol Life Sci 63(14):1579–1585

    Article  CAS  Google Scholar 

  2. Pelosi P, Calvello M, Ban L (2005) Diversity of odorant-binding proteins and chemosensory proteins in insects. Chem Senses 30(suppl 1):i291–i292

    Article  CAS  Google Scholar 

  3. Pelosi P, Zhou JJ, Ban L, Calvello M (2006) Soluble proteins in insect chemical communication. Cell Mol Life Sci 63(14):1658–1676

    Article  CAS  Google Scholar 

  4. Pelosi P, Maida R (1995) Odorant-binding proteins in insects. Comp Biochem Physiol B 111(3):503–514

    Article  CAS  Google Scholar 

  5. Zhou JJ (2010) Odorant-binding proteins in insects. Vitam Horm 83:241–272

    Article  CAS  Google Scholar 

  6. Chandre F, Darriet F, Darder M, Cuany A, Doannio J, Pasteur N, Guillet P (1998) Pyrethroid resistance in Culex quinquefasciatusfrom West Africa. Med Vet Entomol 12(4):359–366

    Article  CAS  Google Scholar 

  7. Barbosa RMR, Furtado A, Regis L, Leal WS (2010) Evaluation of an oviposition stimulating kairomone for the yellow fever mosquito, Aedes aegypti, in Recife, Brazil. J Vector Ecol 35(1):204–207

    Article  Google Scholar 

  8. Leal WS, Barbosa R, Xu W, Ishida Y, Syed Z, Latte N, Chen AM, Morgan TI, Cornel AJ, Furtado A (2008) Reverse and conventional chemical ecology approaches for the development of oviposition attractants for Culex mosquitoes. PLoS One 3(8):e3045

    Article  Google Scholar 

  9. Horst R, Damberger F, Luginbühl P, Güntert P, Peng G, Nikonova L, Leal WS, Wüthrich K (2001) NMR structure reveals intramolecular regulation mechanism for pheromone binding and release. Proc Natl Acad Sci U S A 98(25):14374

    Article  CAS  Google Scholar 

  10. Leal WS, Chen AM, Erickson ML (2005) Selective and pH-dependent binding of a moth pheromone to a pheromone-binding protein. J Chem Ecol 31(10):2493–2499

    Article  CAS  Google Scholar 

  11. Gräter F, de Groot BL, Jiang H, Grubmüller H (2006) Ligand-release pathways in the pheromone-binding protein of Bombyx mori. Structure 14(10):1567–1576

    Article  Google Scholar 

  12. Leite NR, Krogh R, Xu W, Ishida Y, Iulek J, Leal WS, Oliva G (2009) Structure of an odorant-binding protein from the mosquito Aedes aegypti suggests a binding pocket covered by a pH-sensitive “lid”. PLoS One 4(11):e8006

    Article  Google Scholar 

  13. Mao Y, Xu X, Xu W, Ishida Y, Leal WS, Ames JB, Clardy J (2010) Crystal and solution structures of an odorant-binding protein from the southern house mosquito complexed with an oviposition pheromone. Proc Natl Acad Sci U S A 107(44):19102

    Article  CAS  Google Scholar 

  14. Mertz JE, Pettitt BM (1994) Molecular dynamics at a constant pH. Int J High Perform Comput Appl 8(1):47

    Article  Google Scholar 

  15. Baptista AM, Martel PJ, Petersen SB (1997) Simulation of protein conformational freedom as a function of pH: constant pH molecular dynamics using implicit titration. Proteins 27(4):523–544

    Article  CAS  Google Scholar 

  16. Börjesson U, Hünenberger PH (2001) Explicit-solvent molecular dynamics simulation at constant pH: methodology and application to small amines. J Chem Phys 114:9706

    Article  Google Scholar 

  17. Börjesson U, Hünenberger PH (2004) pH-dependent stability of a decalysine α-helix studied by explicit-solvent molecular dynamics simulations at constant pH. J Phys Chem B 108(35):13551–13559

    Article  Google Scholar 

  18. Khandogin J, Brooks CL (2005) Constant pH molecular dynamics with proton tautomerism. Biophys J 89(1):141–157

    Article  CAS  Google Scholar 

  19. Lee MS (2004) Constant-pH molecular dynamics using continuous titration coordinates. Proteins 56:738–752

    Article  CAS  Google Scholar 

  20. Khandogin J, Brooks CL (2007) Linking folding with aggregation in Alzheimer’s α-amyloid peptides. Proc Natl Acad Sci U S A 104(43):16880

    Article  CAS  Google Scholar 

  21. Khandogin J, Chen J, Brooks CL (2006) Exploring atomistic details of pH-dependent peptide folding. Proc Natl Acad Sci U S A 103(49):18546

    Article  CAS  Google Scholar 

  22. Mongan J, Case DA, McCammon JA (2004) Constant pH molecular dynamics in generalized born implicit solvent. J Comput Chem 25(16):2038–2048

    Article  CAS  Google Scholar 

  23. Baptista AM, Teixeira VH, Soares CM (2002) Constant-pH molecular dynamics using stochastic titration. J Chem Phys 117:4184

    Article  CAS  Google Scholar 

  24. Machuqueiro M, Baptista AM (2006) Constant-pH molecular dynamics with ionic strength effects: protonation-conformation coupling in decalysine. J Phys Chem B 110(6):2927–2933

    Article  CAS  Google Scholar 

  25. Machuqueiro M, Baptista AM (2009) Molecular dynamics at constant pH and reduction potential: application to cytochrome c 3. J Am Chem Soc 131(35):12586–12594

    Article  CAS  Google Scholar 

  26. Bürgi R, Kollman PA, van Gunsteren WF (2002) Simulating proteins at constant pH: an approach combining molecular dynamics and Monte Carlo simulation. Protein Struct Funct Bioinforma 47(4):469–480

    Article  Google Scholar 

  27. Dlugosz M, Antosiewicz J (2005) Effects of solute-solvent proton exchange on polypeptide chain dynamics: a constant-pH molecular dynamics study. J Phys Chem B 109(28):13777–13784

    Article  CAS  Google Scholar 

  28. Walczak AM, Antosiewicz JM (2002) Langevin dynamics of proteins at constant pH. Phys Rev E 66(5):051911

    Article  Google Scholar 

  29. Williams SL, De Oliveira CAF, McCammon JA (2010) Coupling constant pH molecular dynamics with accelerated molecular dynamics. J Chem Theory Comput 6(2):560–568

    Article  CAS  Google Scholar 

  30. Meng Y, Roitberg AE (2010) Constant pH replica exchange molecular dynamics in biomolecules using a discrete protonation model. J Chem Theory Comput 6(4):1401–1412

    Article  CAS  Google Scholar 

  31. Bashford D, Case DA (2000) Generalized born models of macromolecular solvation effects. Annu Rev Phys Chem 51(1):129–152

    Article  CAS  Google Scholar 

  32. Onufriev A, Bashford D, David A (2000) Modification of the generalized born model suitable for macromolecules. J Phys Chem B 104(15):3712–3720

    Article  CAS  Google Scholar 

  33. Case DA, Darden T, Cheatham III TE, Simmerling C, Wang J, Duke RE, Luo R, Crowley M, Walker R, Zhang W (2008) Amber 10 users manual. University of California

  34. Onufriev A, Case DA, Bashford D (2002) Effective Born radii in the generalized born approximation: the importance of being perfect. J Comput Chem 23(14):1297–1304

    Article  CAS  Google Scholar 

  35. Onufriev A, Bashford D, Case DA (2004) Exploring protein native states and large-scale conformational changes with a modified generalized born model. Proteins 55(2):383–394

    Article  CAS  Google Scholar 

  36. Berendsen HJC, Postma JPM, Van Gunsteren WF, DiNola A, Haak J (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81:3684

    Article  CAS  Google Scholar 

  37. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30(16):2785–2791

    Article  CAS  Google Scholar 

  38. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19(14):1639–1662

    Article  CAS  Google Scholar 

  39. Sham YY, Muegge I, Warshel A (1998) The effect of protein relaxation on charge-charge interactions and dielectric constants of proteins. Biophys J 74(4):1744–1753

    Article  CAS  Google Scholar 

  40. Simonson T, Archontis G, Karplus M (1999) A Poisson-Boltzmann study of charge insertion in an enzyme active site: the effect of dielectric relaxation. J Phys Chem B 103(29):6142–6156

    Article  CAS  Google Scholar 

  41. Warshel A, Aqvist J (1991) Electrostatic energy and macromolecular function. Annu Rev Biophys Biophys Chem 20(1):267–298

    Article  CAS  Google Scholar 

  42. Lautenschlager C, Leal WS, Clardy J (2005) Coil-to-helix transition and ligand release of Bombyx mori pheromone-binding protein. Biochem Biophys Res Commun 335(4):1044–1050

    Article  CAS  Google Scholar 

  43. Xu W, Leal WS (2008) Molecular switches for pheromone release from a moth pheromone-binding protein. Biochem Biophys Res Commun 372(4):559–564

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by Natural Science Foundation of China, Specialized Research Fund for the Doctoral Program of Higher Education, and Specialized Fund for the Basic Research of Jilin University (Grant Nos. 20903045, 20573042, 20070183046, and 200810018).

Author information

Authors and Affiliations

  1. State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, People’s Republic of China

    Wen-Ting Chu, Ji-Long Zhang, Qing-Chuan Zheng, Lin Chen, Yun-Jian Wu, Qiao Xue & Hong-**ng Zhang

Authors
  1. Wen-Ting Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ji-Long Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qing-Chuan Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun-Jian Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiao Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hong-**ng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Qing-Chuan Zheng or Hong-**ng Zhang.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 283 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chu, WT., Zhang, JL., Zheng, QC. et al. Constant pH molecular dynamics (CpHMD) and molecular docking studies of CquiOBP1 pH-induced ligand releasing mechanism. J Mol Model 19, 1301–1309 (2013). https://doi.org/10.1007/s00894-012-1680-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00894-012-1680-0

Keywords

Search

Navigation