The Energy Landscape

  • H. Frauenfelder
  • B. H. McMahon
Part of the Springer Series in Chemical Physics book series (CHEMICAL, volume 67)


If proteins existed in unique structures, with each atom always in the same place, there would be no need to introduce the concepts of an energy landscape and of conformational substates. Single protein experiments would give the same results as experiments on ensembles and would therefore be unnecessary; this Nobel conference would not have taken place. Proteins would be rigid and could not function. In reality, proteins can assume a very large number of somewhat different conformations [1, 2]. In some cases, such as prions and ameloid fibers, the protein conformation may change completely. In other cases, conformational motions activate enzymes, permit access to active sites, or cleave chemical bonds. The energy landscape is the conceptual framework in which these motions and reactions can be described. Here we sketch the experiments that led us to the concepts of substates and landscapes and describe their importance for the interpretation of single-molecule experiments. For surveys, see for instance the papers presented at a conference on landscapes [3]. Some of the data and concepts treated here were discussed from a different point of view [4] at an earlier Nobel Symposium on Structure and Dynamics of Biological Systems.


Rate Coefficient Energy Landscape Conformational Motion Ensemble Experiment Spectral Hole Burning 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    K. U. Linderstrøm-Lang and J. A. Schellman, Enzymes 1, 443 (1959)Google Scholar
  2. 2.
    I. M. Klotz, Arch. Biochem. Biophys. 116, 92 (1966)Google Scholar
  3. 3.
    H. Frauenfelder, A. R. Bishop, et al., Landscape Paradigms in Physics and Biology-Concepts, Structures, and Dynamics (North-Holland, Amsterdam, 1997)Google Scholar
  4. 4.
    H. Frauenfelder, P. J. Steinbach, and R. D. Young, Chemica Scripta 29A, 145–150 (Nobel Symposium 71, Structure and Dynamics of Biological Systems B) (1989)Google Scholar
  5. 5.
    R. H. Austin et al., Phys. Rev. Lett. 32, 403–405 (1974)ADSCrossRefGoogle Scholar
  6. 6.
    R. H. Austin et al., Biochem. 14, 5355 (1975)CrossRefGoogle Scholar
  7. 7.
    H. Frauenfelder, Methods of Enzymology 54, 506–532 (1978)CrossRefGoogle Scholar
  8. 8.
    A. E. Garcia, R. Blumenfeld, G. Hummer, and J. A. Krumhansl, Physica D 107, 225–239 (1997)ADSCrossRefGoogle Scholar
  9. 9.
    H. Frauenfelder, G. U. Nienhaus, and R. D. Young, Disorder Effects on Relaxational Processes, Richter and Blumen (eds.), pp. 591–614 (Springer, Berlin, 1994)CrossRefGoogle Scholar
  10. 10.
    G. U. Nienhaus and R. D. Young, Encyclopedia of Applied Physics 15, 163–184 (1996)Google Scholar
  11. 11.
    A. E. Garcia, J. A. Krumhansl, and H. Frauenfelder, Proteins 29, 153–160 (1997)CrossRefGoogle Scholar
  12. 12.
    H. Frauenfelder, G. A. Petsko, and D. Tsernoglou, Nature 280, 331 (1979)CrossRefGoogle Scholar
  13. 13.
    G. A. Petsko and D. Ringe, Ann. Rev. Biophys. Bioeng. 17, 451 (1984)Google Scholar
  14. 14.
    P. A. Rejto and S. T. Freer, Progr. Biophys. Molec. Biol. 66, 167–196 (1996)CrossRefGoogle Scholar
  15. 15.
    J. Friedrich, Methods in Enzymology 246, 226–259 (1995)CrossRefGoogle Scholar
  16. 16.
    D. Kleinfeld, N. Okamura, and G. Feher, Biochem. 23, 5780–5786 (1984)CrossRefGoogle Scholar
  17. 17.
    B. H. McMahon, J. D. Müller, C. A. Wraight, and G. U. Nienhaus, Biophys. J. 74, 2567–2587 (1998)ADSCrossRefGoogle Scholar
  18. 18.
    J. M. Peloquin et al., Biochem. 33, 8089–8100 (1994)CrossRefGoogle Scholar
  19. 19.
    A. Ansari et al., Proc. Natl. Acad. Sci. USA 82, 5000–5004 (1985)ADSCrossRefGoogle Scholar
  20. 20.
    H. Frauenfelder, S. G. Sligar, and P. G. Wolynes, Science 254, 1598–1603 (1991)ADSCrossRefGoogle Scholar
  21. 21.
    M. W. Makinen, R. A. Houtchens, and W. S. Caughey, Proc. Natl. Acad. Sci. USA 76, 6042–6046 (1979)ADSCrossRefGoogle Scholar
  22. 22.
    J. O. Alben et al., Proc. Natl. Acad. Sci. USA 79, 3744–3748 (1982)ADSCrossRefGoogle Scholar
  23. 23.
    J. B. Johnson et al., Biophys. J. 71, 1563–1573 (1996)ADSCrossRefGoogle Scholar
  24. 24.
    A. Ansari et al., Biophys. Chem. 26, 337–355 (1987)CrossRefGoogle Scholar
  25. 25.
    D. Thorn Leeson et al., J. Phys. Chem. 101, 6331–6340 (1997)CrossRefGoogle Scholar
  26. 26.
    P. W. Anderson, B. I. Halperin, and C. M. Varma, Phil. Mag. 25, 1 (1972)ADSMATHCrossRefGoogle Scholar
  27. 27.
    W. A. Phillips, J. Low Temp. Phys. 7, 351 (1972)ADSCrossRefGoogle Scholar
  28. 28.
    F. Yang and G. N. Phillips Jr., J. Mol. Biol. 256, 762–774 (1996)CrossRefGoogle Scholar
  29. 29.
    J. D. Bryngelson and P. G. Wolynes, J. Phys. Chem. 93, 6902–6915 (1989)CrossRefGoogle Scholar
  30. 30.
    J. N. Onuchic, Z. Luthey-Schulten, and P. G. Wolynes, Ann. Rev. Phys. Chem. 48, 545–600 (1997)ADSCrossRefGoogle Scholar
  31. 31.
    N. Agmon and J. J. Hopfield, J. Chem. Phys. 79, 2042–2053 (1983)ADSCrossRefGoogle Scholar
  32. 32.
    G. U. Nienhaus et al., Proc. Natl. Acad. Sci. USA 89, 2902–2906 (1992)CrossRefGoogle Scholar
  33. 33.
    J. Huang, A. Ridsdale, J. Q. Wang, and J. M. Friedman, Biochem. 36, 14353–14365 (1997)CrossRefGoogle Scholar
  34. 34.
    T. A. Jackson, M. Lim, and P. A. Anfinrud, Chem. Phys. 180, 131–140 (1994)ADSCrossRefGoogle Scholar
  35. 35.
    I. E. T. Iben et al., Phys. Rev. Lett. 62, 1916–1919 (1989)ADSCrossRefGoogle Scholar
  36. 36.
    L. Edman, D. C. Mets, and R. Rigler, Proc. Natl. Acad. Sci. USA 93, 6710–6715 (1996)ADSCrossRefGoogle Scholar
  37. 37.
    Y. W. Jia et al., Proc. Natl. Acad. Sci. USA 94, 7932–7936 (1997)ADSCrossRefGoogle Scholar
  38. 38.
    P. G. Wolynes, J. Res. Natl. Inst. Stand. Technol. 102, 187–194 (1997)CrossRefGoogle Scholar
  39. 39.
    H. Frauenfelder et al., J. Phys. Chem. 94, 1024–1037 (1990)CrossRefGoogle Scholar
  40. 40.
    S. Brawer, Relaxation in Viscous Liquids and Glasses (American Ceramic Society, Columbus, Ohio 1985)Google Scholar
  41. 41.
    S. J. Hagen, J. Hofrichter, and W. A. Eaton, J. Phys. Chem. 100, 12008–12021 (1996)CrossRefGoogle Scholar
  42. 42.
    G. Sartor, E. Mayer, and G. P. Johari, Biophys. J. 66, 249–258 (1994)CrossRefGoogle Scholar
  43. 43.
    R. Zallen, The Physics of Amorphous Solids (Wiley, New York, 1983)CrossRefGoogle Scholar
  44. 44.
    W. A. Phillips, Rep. Prog. Phys. 50, 1657 (1987)ADSCrossRefGoogle Scholar
  45. 45.
    V. I. Goldanskii, I. F. Krupyanski, and V. N. Flerov, Dokl. Akad. Nauk SSSR 272, 23 (1983)MathSciNetGoogle Scholar
  46. 46.
    G. P. Singh et al., Z. Phys. B 55, 23 (1984)ADSCrossRefGoogle Scholar
  47. 47.
    A. Schulte and R. Murray, Phys. Rev. A. 36, 1722 (1987)Google Scholar
  48. 48.
    P. G. Wolynes, J. N. Onuchic, and H. Frauenfelder, to be publishedGoogle Scholar
  49. 49.
    G. I. Makhatadze and P. L. Privalov, Protein Science 5, 507–510 (1996)CrossRefGoogle Scholar
  50. 50.
    C. Tanford, Adv. Protein Chem. 23, 121 (1968)CrossRefGoogle Scholar
  51. 51.
    J. S. Olson et al., J. Am. Chem. Soc. 105, 1522–1527 (1983)CrossRefGoogle Scholar
  52. 52.
    D. Ringe et al., Biochem. 23, 2–4 (1984)CrossRefGoogle Scholar
  53. 53.
    D. A. Case and M. Karplus, J. Mol. Biol. 132, 343–368 (1979)CrossRefGoogle Scholar
  54. 54.
    D. Beece et al., Biochem. 19, 5147–5157 (1980)CrossRefGoogle Scholar
  55. 55.
    T. Kleinert et al., Biochem. 37, 717–733 (1998)CrossRefGoogle Scholar
  56. 56.
    A. Ansari et al., Biochem. 33, 5128–5145 (1994)CrossRefGoogle Scholar
  57. 57.
    J. A. McCammon and S. H. Northrup, Nature 293, 316 (1981)ADSCrossRefGoogle Scholar
  58. 58.
    J. Wang and P. G. Wolynes, Chem. Phys. Lett. 212, 427–433 (1993)ADSCrossRefGoogle Scholar
  59. 59.
    S. S. Xie and J. K. Trautman, Ann. Rev. Phys. Chem. 49, 441–480 (1998)ADSCrossRefGoogle Scholar
  60. 60.
    S. Nie and R. N. Zare, Ann. Rev. Biophys. Biomol. Struct. 26, 567–596 (1997)CrossRefGoogle Scholar
  61. 61.
    P. J. Steinbach et al., Biophys. J. 61, 235–245 (1992)ADSCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • H. Frauenfelder
  • B. H. McMahon

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