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A Physical Picture of Protein Dynamics and Conformational Changes

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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.

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References

  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

    Article  ADS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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. 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

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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. 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

    Article  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  16. Rüffer, R., Chumakov, A.I.: Nuclear inelastic scattering. Hyperfine Interact. 128, 255–272 (2000). doi:10.1023/A:1012643918108

    Article  ADS  Google Scholar 

  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)

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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. 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)

    ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  24. Parak, F., Reinisch, L.: Mössbauer effect in the study of structure dynamics. Methods Enzymol. 131, 568–607 (1986)

    Article  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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. 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

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  33. Albanese, G., Deriu, A.: High energy resolution X-ray spectroscopy. Riv. Nuovo Cimento 2, 1–39 (1979)

    MathSciNet  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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. 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. 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

    Article  ADS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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)

    ADS  Google Scholar 

  42. Stryer, L.: Biochemistry. Freeman, New York (1995)

    Google Scholar 

  43. Kramers, H.A.: Brownian motion in a field of force and the diffusion model of chemical reactions. Physica 7(4), 284–304 (1940)

    Article  MATH  ADS  MathSciNet  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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

    Article  Google Scholar 

  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)

    ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

  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)

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  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)

    ADS  Google Scholar 

  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

    Article  ADS  Google Scholar 

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Authors and Affiliations

  1. Physik-Department E17, Technische Universität München, 85747, Garching, Germany

    Fritz G. Parak, Klaus Achterhold, Simonetta Croci & Marius Schmidt

  2. Sezione di Fisica, Dipartimento di Sanità Pubblica, Università di Parma, Via Volturno 39, 43100, Parma, Italy

    Simonetta Croci

  3. Department of Physics, University of Wisconsin-Milwaukee, E. Kenwood Blvd, Milwaukee, WI, 53211, USA

    Marius Schmidt

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  1. Fritz G. Parak
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Parak, F.G., Achterhold, K., Croci, S. et al. A Physical Picture of Protein Dynamics and Conformational Changes. J Biol Phys 33, 371–387 (2007). https://doi.org/10.1007/s10867-008-9102-3

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