Journal of Biological Physics

, 33:371

A Physical Picture of Protein Dynamics and Conformational Changes

  • Fritz G. Parak
  • Klaus Achterhold
  • Simonetta Croci
  • Marius Schmidt
Original Paper

Abstract

A physical model is reviewed which explains different aspects of protein dynamics consistently. At low temperatures, the molecules are frozen in conformational substates. Their average energy is 3/2RT. Solid-state vibrations occur on a time scale of femtoseconds to nanoseconds. Above a characteristic temperature, often called the dynamical transition temperature, slow modes of motions can be observed occurring on a time scale between about 140 and 1 ns. These motions are overdamped, quasidiffusive, and involve collective motions of segments of the size of an α-helix. Molecules performing these types of motion are in the “flexible state”. This state is reached by thermal activation. It is shown that these motions are essential for conformational relaxation. Based on this picture, a new approach is proposed to understand conformational changes. It connects structural fluctuations and conformational transitions.

Keywords

Protein dynamics Conformational relaxation Mössbauer effect Myoglobin 

References

  1. 1.
    Austin, R.H., Beeson, K., Eisenstein, L., Frauenfelder, H., Gunsalus, I.C., Marshall, V.P.: Activation energy spectrum of a molecule: photodissociation of carbonmonoxy myoglobin at low temperatures. Phys. Rev. Lett. 32, 403–405 (1974). doi:10.1103/PhysRevLett.32.403 CrossRefADSGoogle Scholar
  2. 2.
    Austin, R.H., Beeson, K.W., Eisenstein, L., Frauenfelder, H., Gunsalus, I.C.: Dynamics of ligand binding to myoglobin. Biochemistry 14, 5355–5373 (1975). doi:10.1021/bi00695a021 CrossRefGoogle Scholar
  3. 3.
    Ansari, A., Berendzen, J., Bowne, S.F., Frauenfelder, H., Iben, I.E.T., Sauke, T.B., Shyamsunder, E., Young, R.D.: Protein states and proteinquakes. Proc. Natl. Acad. Sci. USA 82, 5000–5004 (1985). doi:10.1073/pnas.82.15.5000 CrossRefADSGoogle Scholar
  4. 4.
    Ostermann, A., Waschipky, R., Parak, F.G., Nienhaus, G.U.: Ligand binding and conformational motions in myoglobin. Nature 404, 205–208 (2000). doi:10.1038/35004622 CrossRefADSGoogle Scholar
  5. 5.
    Frauenfelder, H., Parak, F., Young, R.D.: Conformational substates in proteins. Annu. Rev. Biophys. Biophys. Chem. 17, 451–479 (1988). doi:10.1146/annurev.bb.17.060188.002315 CrossRefGoogle Scholar
  6. 6.
    Kendrew, J.C., Dickerson, R.E., Strandberg, B.E., Hart, R.G., Davies, D.R., Phillips, D.C., Shore, V.C.: Structure of myoglobin: a three-dimensional Fourier synthesis at 2 Angstrom resolution. Nature 185, 422–427 (1960). doi:10.1038/185422a0 CrossRefADSGoogle Scholar
  7. 7.
    Vojtechovský, J., Chu, K., Berendzen, J., Sweet, R.M., Schlichting, I.: Crystal structures of myoglobin-ligand complexes at near-atomic resolution. Biophys. J. 77, 2153–2174 (1999)Google Scholar
  8. 8.
    Frauenfelder, H., Petsko, G.A., Tsernoglou, D.: Temperature-dependent X-ray diffraction as a probe of protein structural dynamics. Nature 280, 558–563 (1979). doi:10.1038/280558a0 CrossRefADSGoogle Scholar
  9. 9.
    Artymiuk, P.J., Blake, C.C.F., Grace, D.E.P., Oatly, S.J., Phillips, M.D.C., Sternberg, M.J.E.: Crysatallographic studies of the dynamic properties of lysozyme. Nature 280, 563–568 (1979). doi:10.1038/280563a0 CrossRefADSGoogle Scholar
  10. 10.
    Parak, F., Hartmann, H., Aumann, K.D., Reuscher, H., Rennekamp, G., Bartunik, H., Steigemann, W.: Low temperature X-ray investigation of structural distributions in myoglobin. Eur. Biophys. J. 15, 237–249 (1987). doi:10.1007/BF00577072 CrossRefGoogle Scholar
  11. 11.
    Kidera, A., Go, N.: Normal mode refinement: crystallographic refinement of protein dynamic structure—I. Theory and test by simulated diffraction data. J. Mol. Biol. 225, 457–475 (1992). doi:10.1016/0022-2836(92)90932-A CrossRefGoogle Scholar
  12. 12.
    Kidera, A., Inaka, K., Matsushima, M., Go, N.: Normal mode refinement: crystallographic refinement of protein dynamic structure—II. Application to human lysozyme. J. Mol. Biol. 225, 477–475 (1992). doi:10.1016/0022-2836(92)90933-B Google Scholar
  13. 13.
    Chong, S.-H., Joti, Y., Kidera, A., Go, N., Ostermann, A., Gassmann, A., Parak, F.: Dynamical transition of myoglobin in a crystal: comparative studies of X-ray crystallography and Mössbauer spectroscopy. Eur. Biophys. J. 30, 319–329 (2001). doi:10.1007/s002490100152 CrossRefGoogle Scholar
  14. 14.
    Sturhahn, W., Toellner, T.S., Alp, E.E., Zhang, X., Ando, M., Yoda, Y., Kikuta, S., Seto, M., Kimball, C.W., Dabrowski, B.: Phonon density of states measured by inelastic resonant scattering. Phys. Rev. Lett. 74, 3832–3835 (1995). doi:10.1103/PhysRevLett.74.3832 CrossRefADSGoogle Scholar
  15. 15.
    Seto, M., Yoda, Y., Kikuta, S., Zhang, X.W., Ando, M.: Observation of nuclear resonant scattering accompanied by phonon excitation using synchrotron radiation. Phys. Rev. Lett. 74, 3828–3831 (1995). doi:10.1103/PhysRevLett.74.3828 CrossRefADSGoogle Scholar
  16. 16.
    Rüffer, R., Chumakov, A.I.: Nuclear inelastic scattering. Hyperfine Interact. 128, 255–272 (2000). doi:10.1023/A:1012643918108 CrossRefADSGoogle Scholar
  17. 17.
    Achterhold, K., Keppler, C., Ostermann, A., van Bürck, U., Sturhahn, W., Alp, E.E., Parak, F.G.: Vibrational dynamics of myoglobin determined by phonon-assisted Mössbauer effect. Phys. Rev. E 65, 051916-1–051916-13 (2002)CrossRefADSGoogle Scholar
  18. 18.
    Achterhold, K., Sturhahn, W., Alp, E.E., Parak, F.G.: Phonon-assisted Mössbauer effect: the vibrational density of states of myoglobin. Hyperfine Interact. 141/142, 3–12 (2002). doi:10.1023/A:1021254003628 CrossRefADSGoogle Scholar
  19. 19.
    Maradudin, A.A., Montroll, E.W., Weiss, G.H.: Theory of lattice dynamics in the harmonic approximation. In: Seitz, F., Turnball, D. (eds.) Solid State Physics. Academic Press, New York (1963)Google Scholar
  20. 20.
    Melchers, B., Knapp, E.W., Parak, F., Cordone, L., Cupane, A., Leone, M.: Structual fluctuations of myoglobin from normal-modes, Mössbauer, Raman, and absorption spectroscopy. Biophys. J. 70, 2092–2099 (1996)ADSGoogle Scholar
  21. 21.
    Parak, F., Formanek, H.: Untersuchung des Schwingungsanteils und des Kristallgitterfehleranteils des Temperaturfaktors in Myoglobin durch Vergleich von Mössbauerabsorptionsmessungen mit Röntgenstrukturdaten. Acta Crystallogr. A 27, 573–578 (1971). doi:10.1107/S0567739471001281 CrossRefADSGoogle Scholar
  22. 22.
    Parak, F., Frolov, E.N., Mössbauer, R.L., Goldanskii, V.I.: Dynamics of metmyoglobin crystals investigated by nuclear gamma resonance absorption. J. Mol. Biol. 145, 825–833 (1981). doi:10.1016/0022-2836(81)90317-X CrossRefGoogle Scholar
  23. 23.
    Parak, F., Knapp, E.W., Kucheida, D.: Protein dynamics: Mössbauer spectroscopy on deoxymyoglobin crystals. J. Mol. Biol. 161, 177–194 (1982). doi:10.1016/0022-2836(82)90285-6 CrossRefGoogle Scholar
  24. 24.
    Parak, F., Reinisch, L.: Mössbauer effect in the study of structure dynamics. Methods Enzymol. 131, 568–607 (1986)CrossRefGoogle Scholar
  25. 25.
    Knapp, E.W., Fischer, S.F., Parak, F.: The influence of protein dynamics of Mössbauer spectra. J. Chem. Phys. 78, 4701–4711 (1983). doi:10.1063/1.445316 CrossRefADSGoogle Scholar
  26. 26.
    Knapp, E.W., Fischer, S.F., Parak, F.: Protein dynamics from Mössbauer spectra. The temperature dependence. J. Phys. Chem. 86(26), 5042–5047 (1982). doi:10.1021/j100223a002 CrossRefGoogle Scholar
  27. 27.
    Parak, F., Knapp, E.W.: A consistent picture of protein dynamics. Proc. Natl. Acad. Sci. USA 81, 7088–7092 (1984). doi:10.1073/pnas.81.22.7088 CrossRefADSGoogle Scholar
  28. 28.
    Parak, F., Heidemeier, J., Knapp, E.W.: Brownian motions in molecular networks. In: Chin, E.C.S. (ed.) Biological and Artificial Intelligence Systems, pp. 23–48. ESCOM, Leiden (1988)Google Scholar
  29. 29.
    Huenges, A., Achterhold, K., Parak, F.G.: Mössbauer spectroscopy in the energy and in the time domain, a crucial tool for the investigation of protein dynamics. Hyperfine Interact. 144/145, 209–222 (2002). doi:10.1023/A:1025405805908 CrossRefADSGoogle Scholar
  30. 30.
    Doster, W., Cusack, S., Petry, W.: Dynamical transition of myoglobin revealed by inelastic neutron scattering. Nature 337, 754–756 (1989). doi:10.1038/337754a0 CrossRefADSGoogle Scholar
  31. 31.
    Engler, N., Ostermann, A., Niimura, N., Parak, F.G.: Hydrogen atoms in proteins – positions and dynamics. Proc. Natl. Acad. Sci. USA 100, 10243–10248 (2003). doi:10.1073/pnas.1834279100 CrossRefADSGoogle Scholar
  32. 32.
    Champeney, D.C.: The scattering of Mössbauer radiation by condensed matter. Rep. Prog. Phys. 42, 1017–1054 (1979). doi:10.1088/0034-4885/42/6/002 CrossRefADSGoogle Scholar
  33. 33.
    Albanese, G., Deriu, A.: High energy resolution X-ray spectroscopy. Riv. Nuovo Cimento 2, 1–39 (1979)MathSciNetGoogle Scholar
  34. 34.
    Nienhaus, G.U., Heinzl, J., Huenges, E., Parak, F.: Protein crystal dynamics studied by time-resolved analysis of X-ray diffuse scattering. Nature 338, 665–666 (1989). doi:10.1038/338665a0 CrossRefADSGoogle Scholar
  35. 35.
    Parak, F., Achterhold, K., Hartmann, H., Heinzl, J., Huenges, E., Nienhaus, G.U.: Rayleigh scattering of Mössbauer radiation on a myoglobin single crystal. Hyperfine Interact. 71, 1319–1322 (1992). doi:10.1007/BF02397327 CrossRefADSGoogle Scholar
  36. 36.
    Krupyanskii, Y.F., Parak, F., Gaubman, E.E., Wagner, F.M., Goldanskii, V.I., Mössbauer, R.L., Suzdalev, I.P., Litterst, F.J., Vogel, H.: Investigation of the dynamics of metmyoglobin by Rayleigh scattering of Mössbauer radiation (RSMR). J. de Physique 41, C1–489–C1–490 (1980)Google Scholar
  37. 37.
    Krupyanskii, Y.F., Parak, F., Goldanskii, V.I., Mössbauer, R.L., Gaubman, E.E., Engelmann, H., Suzdalev, I.P.: Investigation of large intramolecular movements within metmyoglobin by Rayleigh scattering of Mössbauer radiation (RSMR). Z. Naturforsch. [C] 37c, 57–62 (1982)Google Scholar
  38. 38.
    Nienhaus, G.U., Hartmann, H., Parak, F., Heinzl, J., Huenges, E.: Angular dependent Rayleigh scattering of Mössbauer radiation on proteins. Hyperfine Interact. 47, 299–310 (1989). doi:10.1007/BF02351614 CrossRefADSGoogle Scholar
  39. 39.
    Lamb, D.C., Ostermann, A., Prusakov, V.E., Parak, F.G.: From metmyoglobin to deoxy myoglobin: relaxations of an intermediate state. Eur. Biophys. J. 27, 113–125 (1998). doi:10.1007/s002490050117 CrossRefGoogle Scholar
  40. 40.
    Lamb, D.C., Prusakov, V., Engler, N., Ostermann, A., Schellenberg, P., Parak, F.G., Nienhaus, G.U.: Photodissociation and rebinding of H2O to ferrous sperm whale myoglobin. J. Am. Chem. Soc. 120, 2981–2982 (1998). doi:10.1021/ja973781l CrossRefGoogle Scholar
  41. 41.
    Prusakov, V.E., Steyer, J., Parak, F.G.: Mössbauer spectroscopy on nonequilibrium states of myoglobin: a study of r–t relaxation. Biophys. J. 68, 2524–2530 (1995)ADSGoogle Scholar
  42. 42.
    Stryer, L.: Biochemistry. Freeman, New York (1995)Google Scholar
  43. 43.
    Kramers, H.A.: Brownian motion in a field of force and the diffusion model of chemical reactions. Physica 7(4), 284–304 (1940)MATHCrossRefADSMathSciNetGoogle Scholar
  44. 44.
    Hänggi, P., Talkner, P., Borkovec, M.: Reaction-rate theory: fifty years after Kramers. Rev. Mod. Phys. 62(2), 251–342 (1990). doi:10.1103/RevModPhys.62.251 CrossRefADSGoogle Scholar
  45. 45.
    Young, R.D., Bowne, S.F.: Conformational substates and barrier height distributions in ligand binding to heme proteins. J. Chem. Phys. 81, 3730–3737 (1984). doi:10.1063/1.448124 CrossRefADSGoogle Scholar
  46. 46.
    Alvarez, F., Alegria, A., Colmenero, J.: Relationship between the time-domain Kohlrausch–Williams–Watts and frequency-domain Havriliak–Negami relaxation functions. Phys. Rev. B 44(14), 7306–7312 (1991). doi:10.1103/PhysRevB.44.7306 CrossRefADSGoogle Scholar
  47. 47.
    Berberan-Santos, M.N., Bodunov, E.N., Valeur, B.: Mathematical functions for the analysis of luminescence decays with underlying distributions 1. Kohlrausch decay function (stretched exponential). Chem. Phys. 315, 171–182 (2005). doi:10.1016/j.chemphys.2005.04.006 CrossRefADSGoogle Scholar
  48. 48.
    Hartmann, H., Parak, F., Steigemann, W., Petsko, G.A., Ringe Ponzi, D., Frauenfelder, H.: Conformational substates in a protein: structure and dynamics of metmyoglobin at 80 K. Proc. Natl. Acad. Sci. USA 79, 4967–4971 (1982). doi:10.1073/pnas.79.16.4967 CrossRefADSGoogle Scholar
  49. 49.
    Petrova, T., Ginell, S., Mitschler, A., Hazemann, I., Schneider, T., Cousido, A., Lunin, V.Y., Joachimiak, A., Podjarny, A.: Ultrahigh-resolution study of protein atomic displacement parameters at cryotemperatures obtained with a helium cryostat. Acta Crystallogr. D Biol. Crystallogr. 62, 1535–1544 (2006). doi:10.1107/S0907444906041035 CrossRefGoogle Scholar
  50. 50.
    Krupyanskii, Y.F., Kurinov, I.V., Kuznetsov, S.A., Eshenko, G.V., Parak, F.: Dynamics of polyglutamic acids in alpha-helical and coil states. Comparison with dynamics of some globular proteins. Rayleigh scattering of Moessbauer radiation (RSMR) data. Nuovo Cim. 18D, 365–369 (1996)ADSGoogle Scholar
  51. 51.
    Nienhaus, G.U., Mourant, J.R., Frauenfelder, H.: Spectroscopic evidence for conformational relaxation in myoglobin. Proc. Natl. Acad. Sci. USA 89, 2902–2906 (1992). doi:10.1073/pnas.89.7.2902 CrossRefADSGoogle Scholar
  52. 52.
    Engler, N., Ostermann, A., Gassmann, A., Lamb, D.C., Prusakov, V.E., Schott, J., Schweitzer-Stenner, R., Parak, F.G.: Protein dynamics in an intermediate state of myoglobin: optical absorption, resonance Raman spectroscopy, and X-ray structure analysis. Biophys. J. 78, 2081–2092 (2000)CrossRefGoogle Scholar
  53. 53.
    Steinbach, P.J., Ansari, A., Berendzen, J., Braunstein, D., Chu, K., Cowen, B.R., Ehrenstein, D., Frauenfelder, H., Johnson, J.B., Lamb, D.C., Ormos, P., Philipp, R., Xie, A., Young, R.D.: Ligand binding to heme proteins: connection between dynamics and function. Biochemistry 30, 3988–4001 (1991). doi:10.1021/bi00230a026 CrossRefGoogle Scholar
  54. 54.
    Young, R.D., Frauenfelder, H., Johnson, J.B., Lamb, D.C., Nienhaus, G.U., Philipp, R., Scholl, R.: Time- and temperature dependence of large-scale conformational transitions in myoglobin. Chem. Phys. 158, 315–327 (1991). doi:10.1016/0301-0104(91)87075-7 CrossRefGoogle Scholar
  55. 55.
    Mayo, K.H., Parak, F., Mössbauer, R.L.: Observations of elastic and quasi-elastic nuclear gamma resonance absorption in hemoglobin crystals. Phys. Lett. 82A, 468–470 (1981)ADSGoogle Scholar
  56. 56.
    Schmidt, M., Nienhaus, K., Pahl, R., Krasselt, A., Anderson, S., Parak, F., Nienhaus, G.U., Srajer, V.: Ligand migration pathway and protein dynamics in myoglobin: a time-resolved crystallographic study on L29W MbCO. Proc. Nat Acad. Sci. USA 102, 11704–11709 (2005). doi:10.1073/pnas.0504932102 CrossRefADSGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Fritz G. Parak
    • 1
  • Klaus Achterhold
    • 1
  • Simonetta Croci
    • 1
    • 2
  • Marius Schmidt
    • 1
    • 3
  1. 1.Physik-Department E17Technische Universität MünchenGarchingGermany
  2. 2.Sezione di Fisica, Dipartimento di Sanità PubblicaUniversità di ParmaParmaItaly
  3. 3.Department of PhysicsUniversity of Wisconsin-MilwaukeeMilwaukeeUSA

Personalised recommendations