Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Solvent mobility and the protein 'glass' transition

Nature Structural Biology volume 7, pages 34–38 (2000)Cite this article

Abstract

Proteins and other biomolecules undergo a dynamic transition near 200 K to a glass-like solid state with small atomic fluctuations. This dynamic transition can inhibit biological function. To provide a deeper understanding of the relative importance of solvent mobility and the intrinsic protein energy surface in the transition, a novel molecular dynamics simulation procedure with the protein and solvent at different temperatures has been used. Solvent mobility is shown to be the dominant factor in determining the atomic fluctuations above 180 K, although intrinsic protein effects become important at lower temperatures. The simulations thus complement experimental studies by demonstrating the essential role of solvent in controlling functionally important protein fluctuations.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Atomic fluctuations versus residue number.
Figure 2: Cross correlation of atomic fluctuations, averaged by residue over backbone protein atoms.
Figure 3: Mean square fluctuations as a function of distance from the protein surface.

Similar content being viewed by others

References

  1. Karplus, M. & Petsko, G.A. Nature 347, 631–639 (1990).

    Article  CAS  Google Scholar 

  2. Brooks III, C.L., Karplus, M. & Pettitt, B.M. Proteins, A theoretical perspective of dynamics, structure, and thermodynamics. (Wiley, New York; 1988).

    Book  Google Scholar 

  3. Elber, R. & Karplus, M. Science 235, 318–321 (1987).

    Article  CAS  Google Scholar 

  4. Noguti, T. & Go, N. Proteins 5, 104 –112 (1989).

    Article  CAS  Google Scholar 

  5. Frauenfelder, H., Sligar, G.S. & Wolynes, P.G. Science 254, 1598– 1603 (1991).

    Article  CAS  Google Scholar 

  6. Angell, C.A. Science 267, 1924–1935 ( 1995).

    Article  CAS  Google Scholar 

  7. Sokolov, A.P. Science 273, 1675–1676 ( 1996).

    Article  CAS  Google Scholar 

  8. Iben, I.E.T. et al. Phys. Rev. Lett. 62, 1916– 1919 (1989).

    Article  CAS  Google Scholar 

  9. Tilton, R.F., Dewan, J.C. & Petsko, G.A. Biochemistry 31, 2469– 2481 (1992).

    Article  CAS  Google Scholar 

  10. Rasmussen, B.F., Stock, A.M., Ringe, D. & Petsko, G.A. Nature 357, 423–424 (1992).

    Article  CAS  Google Scholar 

  11. Doster, W., Cusack, S. & Petry, W. Nature 337, 754– 756 (1989).

    Article  CAS  Google Scholar 

  12. Smith, J., Kuczera, K. & Karplus, M. Proc. Natl. Acad. Sci. USA 87, 1601–1605 (1990).

    Article  CAS  Google Scholar 

  13. Loncharich, R.J. & Brooks, B.R. J. Mol. Biol. 215, 439–455 ( 1990).

    Article  CAS  Google Scholar 

  14. Austin, R.H., Beeson, K.W., Eisenstein, L., Frauenfelder, H. & Gunsalus, I.C. Biochemistry 14, 5355– 5373 (1975).

    Article  CAS  Google Scholar 

  15. Parak, F., Frolov, E.N., Mössbauer, R.L. & Goldanskii, V.I. J. Mol. Biol. 145, 825–833 (1981).

    Article  CAS  Google Scholar 

  16. Lichtenegger, H. et al. Biophys. J. 76, 414– 422 (1999).

    Article  CAS  Google Scholar 

  17. Laudat, J. & Laudat, F. Europhys. Lett. 20, 663–667 (1992).

    Article  CAS  Google Scholar 

  18. Ding, X., Rasmussen, B.F., Petsko, G.A. & Ringe, D. Biochemistry 33, 9285–9293 (1994).

    Article  CAS  Google Scholar 

  19. Ferrand, M., Dianoux, A.J., Petry, W. & Zaccai, G. Proc. Natl. Acad. Sci. USA 90, 9668–72 ( 1993).

    Article  CAS  Google Scholar 

  20. Norberg, J. & Nilsson, L. Proc. Nat. Acad. Sci. USA 93, 10173–10176 (1996).

    Article  CAS  Google Scholar 

  21. van Gunsteren, W.F. & Karplus, M. Biochemistry 21, 2259–2274 ( 1982).

    Article  CAS  Google Scholar 

  22. Brooks III, C.L. & Karplus, M. J. Mol. Biol. 208, 159–181 (1989).

    Article  CAS  Google Scholar 

  23. Beece, D. et al. Biochemistry 19, 5147– 5157 (1980).

    Article  CAS  Google Scholar 

  24. Ansari, A., Jones, C.M., Henry, E.R., Hofrichter, J. & Eaton, W.A. Science 256, 1796– 1798 (1992).

    Article  CAS  Google Scholar 

  25. Hagen, S.J., Hofrichter, J. & Eaton, W.A. Science 269, 959– 962 (1995).

    Article  CAS  Google Scholar 

  26. Mayer, E. Biophys. J. 67, 862–873 (1994).

    Article  CAS  Google Scholar 

  27. Doster, W., Bachleitner, A., Dunau, R., Hiebl, M. & Luscher, E. Biophys. J. 50, 213–219 (1986).

    Article  CAS  Google Scholar 

  28. Hoover, W.G. Phys. Rev. A 31, 1695–1697 (1985).

    Article  CAS  Google Scholar 

  29. Petsko, G.A. & Ringe, D. Ann. Rev. Biophys. Bioeng. 13, 331–371 (1984).

    Article  CAS  Google Scholar 

  30. Swaminathan, S., Ichiya, T., van Gunsteren, W. & Karplus, M. Biochemistry 21, 5230–5241 (1982).

    Article  CAS  Google Scholar 

  31. Diehl, M., Doster, W., Petry, W. & Schober, H. Biophy. J. 73, 2726–2732 (1997).

    Article  CAS  Google Scholar 

  32. Ichiye, T. & Karplus, M. Proteins 11, 205–217 (1991).

    Article  CAS  Google Scholar 

  33. Settles, M., Post, F., Muller, D., Schulte, A. & Doster, W. Biophys. Chem. 43, 107– 116 (1992).

    Article  CAS  Google Scholar 

  34. Kuczera, K., Kuriyan, J. & Karplus, M. J. Mol. Biol. 213, 351– 373 (1990).

    Article  CAS  Google Scholar 

  35. Hagen, S.J., Hofricher, H.J., Bunn, H.F. & Eaton, W.A. J. French Soc. Blood Trans. 6, 423– 426 (1995).

    Google Scholar 

  36. Jorgensen, W.L., Chandrasekhar, J., Madura, J.D., Impey, R.W. & Klein, M.L. J. Chem. Phys. 79, 926–935 (1983).

    Article  CAS  Google Scholar 

  37. Kuriyan, J., Wilz, S., Karplus, M. & Petsko, G.A. J. Mol. Biol. 192, 133–154 ( 1986).

    Article  CAS  Google Scholar 

  38. Steinbach, P.J. & Brooks, B.R. Proc. Natl. Acad. Sci. 90, 9135–9139 ( 1993).

    Article  CAS  Google Scholar 

  39. Brooks, B.R. et al. J. Comput. Chem. 4, 187– 217 (1983).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Y. Zhou and M.Watanabe for helpful discussions. This work is supported in parts by grants from the National Institute of Health to D.R. and M.K.

Author information

Authors and Affiliations

  1. Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, 02454-9110, Massachusetts, USA

    Dennis Vitkup, Dagmar Ringe & Gregory A. Petsko

  2. Department of Biology, Program in Biophysics and Structural Biology, Brandeis University, Waltham, 02454-9110, Massachusetts , USA

    Dennis Vitkup

  3. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, 02138 , Massachusetts, USA

    Dennis Vitkup & Martin Karplus

  4. Department of Chemistry and Department of Biochemistry, Brandeis University, Waltham, 02454-9110, Massachusetts, USA

    Dagmar Ringe & Gregory A. Petsko

  5. Laboratoire de Chimie Biophysique, Institut le Bel, Universite Louis Pasteur, Strasbourg, 67000, France

    Martin Karplus

Authors
  1. Dennis Vitkup
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dagmar Ringe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gregory A. Petsko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Karplus
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin Karplus.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vitkup, D., Ringe, D., Petsko, G. et al. Solvent mobility and the protein 'glass' transition. Nat Struct Mol Biol 7, 34–38 (2000). https://doi.org/10.1038/71231

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/71231

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing