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Investigation of conformational mobility of insulin superfamily peptides: Use of SPC/E and TIP4P water models

Abstract

A comparative analysis of the two most widely used water models, SPC/E and TIP4P, was carried out. The applicability of the models for studying the conformational mobility of peptides of the insulin superfamily, including proinsulin and insulin-like growth factors (IGF1 and IGF2), was assessed. It was demonstrated that, in the case of both water models, the root-mean-square deviations and the gyration radii tend to exist in the anti-phase; their values only reached a plateau after 9000 ps in the case of IGF1. Additionally, it was shown that, despite maintaining a general type of insulin-like packing structure, the secondary structures were somewhat different when SPC/E and TIP4P were used. These differences could affect the overall dynamics of molecules, as well as their ability to adopt the conformation required to bind with conjugate receptors. We conclude that several, not one, water models should be used to investigate the conformational mobility of peptides.

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Abbreviations

BW:

bulk water

MD:

molecular dynamics

IGF:

insulin-like growth factor

RMSD:

root-mean-square deviation

References

  1. Bagchi B. 2012. From anomalies in neat liquid to structure, dynamics and function in the biological world. Chem. Phys. Lett. 529, 1–9.

    CAS  Article  Google Scholar 

  2. Raschke T.M. 2006. Water structure and interactions with protein surfaces. Curr.Opin. Struct. Biol. 16, 152–159.

    CAS  PubMed  Article  Google Scholar 

  3. Chaplin M. 2006. Do we underestimate the importance of water in cell biology? Nature Rev. Mol. Cell Biol. 7, 861–866.

    CAS  Article  Google Scholar 

  4. Zenin S.V. 1993. Analysis of water structure by the method of proton magnetic resonance. Dokl. Ross. Akad. Nauk. 332, 328–329.

    CAS  Google Scholar 

  5. Ignatov I., Mosin O. 2013. Structural mathematical models describing water clusters. Math. Theory Model. 3, 1–17.

    Google Scholar 

  6. Dyer K.M., Perkyns J.S., Stell G., Pettitt B.M. 2009. Site-renormalized molecular fluid theory: On the utility of a two-site model of water. Mol. Phys. 107, 423–431.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  7. Mark P., Nilsson L. 2001. Structure and dynamics of the TIP3P, SPC, and SPC/E water models at 298 K. J. Phys. Chem. 105, 9954–9960.

    CAS  Article  Google Scholar 

  8. http://www.lsbu.ac.uk/water/models

  9. Krienke H., Opalka D. 2007. Hydration of molecular ions: A molecular dynamics study with a SPC/E water model. J. Phys. Chem. 111, 15935–15941.

    CAS  Google Scholar 

  10. Petrenko V.E., Borovkov A.V., Antipova M.L., Ved’ O.V. 2007. The topological and dynamic characteristics of H-bond networks in water according to computer simulation results. Russ. J. Phys. Chem. 81, 1783–1788.

    CAS  Article  Google Scholar 

  11. Horn H.W., Swope W.C., Pitera J.W., Madura J.D., Dick T.J., Hura G.L., Head-Gordon T. 2004. Development of an improved four-site water model for biomolecular simulations: TIP4P-Ew. J. Chem. Phys. 120, 9665–9678.

    CAS  PubMed  Article  Google Scholar 

  12. Abascal I.L.F., Sanz E., García Fernández R., Vega C. 2005. A potential model for the study of ices and amorphous water: TIP4P/Ice. J. Chem. Phys. 122, 1–9.

    Article  Google Scholar 

  13. Abascal I.L.F., Vega C. 2005. A general purpose model for the condensed phases of water: TIP4P/2005. J. Chem. Phys. 123, 1–12.

    Article  Google Scholar 

  14. Maruyama Y., Harano Y. 2013. Does water drive protein folding? Chem. Phys. Letts. 581, 85–90.

    CAS  Article  Google Scholar 

  15. Levy Y., Wolynes P.G., Onuchic J.N. 2004. Protein topology determines binding mechanism. Proc. Natl. Acad. Sci. U. S. A. 101, 511–516.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  16. Zhang L., Yang Y., Kao Y., Wang L., Zhong D. 2009. Protein hydration dynamics and molecular mechanism of coupled water-protein fluctuations. J. Am. Chem. Soc. 131, 10677–10691.

    CAS  PubMed  Article  Google Scholar 

  17. Jayaram B., Jain T. 2004. The role of water in protein-DNA recognition. Annu. Rev. Biomol. Struct. 33, 343–361.

    CAS  Article  Google Scholar 

  18. Ball P. 2008. Water as an active constituent in cell biology. Chem. Rev. 108, 74–108.

    CAS  PubMed  Article  Google Scholar 

  19. Papoian G.A., Ulander J., Wolynes P.G. 2003. J. Am. Chem. Soc. 125, 9170–9178.

    CAS  PubMed  Article  Google Scholar 

  20. Preininger A.M., Meiler J., Hamm H.E. 2013. J. Mol. Biol. 425, 2288–2298.

    CAS  PubMed  Article  Google Scholar 

  21. Levy Y., Onuchic J.N. 2006. Water mediation in protein folding and molecular recognition. Annu. Rev. Biophys. Biomol. Struct. 35, 389–415.

    CAS  PubMed  Article  Google Scholar 

  22. Hess B., Kutzner C., Spoel D., Lindahl E. 2008. GROMACS 4: Algorithms for highly effecient, load-balanced, and scalable molecular simulations. J. Chem. Theory Comput. 4, 435–447.

    CAS  Article  Google Scholar 

  23. Humphrey W., Dalke A., Schulten K. 1996. VMD: Visual molecular dynamics. J. Mol. Graphics. 14, 33–38.

    CAS  Article  Google Scholar 

  24. Hua Q. 2010. Insulin: A small protein with a long journey. Prot. Cell. 1, 537–551.

    CAS  Article  Google Scholar 

Download references

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Correspondence to O. I. Ksenofontova.

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Original Russian Text © O.I. Ksenofontova, 2014, published in Molekulyarnaya Biologiya, 2014, Vol. 48, No. 3, pp. 500–507.

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Ksenofontova, O.I. Investigation of conformational mobility of insulin superfamily peptides: Use of SPC/E and TIP4P water models. Mol Biol 48, 432–438 (2014). https://doi.org/10.1134/S0026893314030121

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  • DOI: https://doi.org/10.1134/S0026893314030121

Keywords

  • water models
  • TIP4P
  • SPC/E
  • conformational mobility
  • insulin superfamily peptides
  • computer simulation