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. 2000 Dec;79(6):3244–3257. doi: 10.1016/S0006-3495(00)76557-X

The dynamics of protein hydration water: a quantitative comparison of molecular dynamics simulations and neutron-scattering experiments.

M Tarek 1, D J Tobias 1
PMCID: PMC1301199  PMID: 11106628

Abstract

We present results from an extensive molecular dynamics simulation study of water hydrating the protein Ribonuclease A, at a series of temperatures in cluster, crystal, and powder environments. The dynamics of protein hydration water appear to be very similar in crystal and powder environments at moderate to high hydration levels. Thus, we contend that experiments performed on powder samples are appropriate for discussing hydration water dynamics in native protein environments. Our analysis reveals that simulations performed on cluster models consisting of proteins surrounded by a finite water shell with free boundaries are not appropriate for the study of the solvent dynamics. Detailed comparison to available x-ray diffraction and inelastic neutron-scattering data shows that current generation force fields are capable of accurately reproducing the structural and dynamical observables. On the time scale of tens of picoseconds, at room temperature and high hydration, significant water translational diffusion and rotational motion occur. At low hydration, the water molecules are translationally confined but display appreciable rotational motion. Below the protein dynamical transition temperature, both translational and rotational motions of the water molecules are essentially arrested. Taken together, these results suggest that water translational motion is necessary for the structural relaxation that permits anharmonic and diffusive motions in proteins. Furthermore, it appears that the exchange of protein-water hydrogen bonds by water rotational/librational motion is not sufficient to permit protein structural relaxation. Rather, the complete exchange of protein-bound water molecules by translational displacement seems to be required.

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Selected References

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  1. Angell C. A. Formation of glasses from liquids and biopolymers. Science. 1995 Mar 31;267(5206):1924–1935. doi: 10.1126/science.267.5206.1924. [DOI] [PubMed] [Google Scholar]
  2. Badger J., Caspar D. L. Water structure in cubic insulin crystals. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):622–626. doi: 10.1073/pnas.88.2.622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barron L. D., Hecht L., Wilson G. The lubricant of life: a proposal that solvent water promotes extremely fast conformational fluctuations in mobile heteropolypeptide structure. Biochemistry. 1997 Oct 28;36(43):13143–13147. doi: 10.1021/bi971323j. [DOI] [PubMed] [Google Scholar]
  4. Bryant R. G. The dynamics of water-protein interactions. Annu Rev Biophys Biomol Struct. 1996;25:29–53. doi: 10.1146/annurev.bb.25.060196.000333. [DOI] [PubMed] [Google Scholar]
  5. Burling F. T., Weis W. I., Flaherty K. M., Brünger A. T. Direct observation of protein solvation and discrete disorder with experimental crystallographic phases. Science. 1996 Jan 5;271(5245):72–77. doi: 10.1126/science.271.5245.72. [DOI] [PubMed] [Google Scholar]
  6. Denisov V. P., Halle B. Protein hydration dynamics in aqueous solution. Faraday Discuss. 1996;(103):227–244. doi: 10.1039/fd9960300227. [DOI] [PubMed] [Google Scholar]
  7. Denisov V. P., Halle B. Protein hydration dynamics in aqueous solution: a comparison of bovine pancreatic trypsin inhibitor and ubiquitin by oxygen-17 spin relaxation dispersion. J Mol Biol. 1995 Feb 3;245(5):682–697. doi: 10.1006/jmbi.1994.0055. [DOI] [PubMed] [Google Scholar]
  8. Denisov V. P., Halle B. Thermal denaturation of ribonuclease A characterized by water 17O and 2H magnetic relaxation dispersion. Biochemistry. 1998 Jun 30;37(26):9595–9604. doi: 10.1021/bi980442b. [DOI] [PubMed] [Google Scholar]
  9. Doster W, Cusack S, Petry W. Dynamic instability of liquidlike motions in a globular protein observed by inelastic neutron scattering. Phys Rev Lett. 1990 Aug 20;65(8):1080–1083. doi: 10.1103/PhysRevLett.65.1080. [DOI] [PubMed] [Google Scholar]
  10. Ferrand M., Dianoux A. J., Petry W., Zaccaï G. Thermal motions and function of bacteriorhodopsin in purple membranes: effects of temperature and hydration studied by neutron scattering. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9668–9672. doi: 10.1073/pnas.90.20.9668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fitter J., Lechner R. E., Dencher N. A. Picosecond molecular motions in bacteriorhodopsin from neutron scattering. Biophys J. 1997 Oct;73(4):2126–2137. doi: 10.1016/S0006-3495(97)78243-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fitter J. The temperature dependence of internal molecular motions in hydrated and dry alpha-amylase: the role of hydration water in the dynamical transition of proteins. Biophys J. 1999 Feb;76(2):1034–1042. doi: 10.1016/S0006-3495(99)77268-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Frick B., Richter D. The microscopic basis of the glass transition in polymers from neutron scattering studies. Science. 1995 Mar 31;267(5206):1939–1945. doi: 10.1126/science.267.5206.1939. [DOI] [PubMed] [Google Scholar]
  14. Gallo P, Sciortino F, Tartaglia P, Chen S. Slow dynamics of water molecules in supercooled states. Phys Rev Lett. 1996 Apr 8;76(15):2730–2733. doi: 10.1103/PhysRevLett.76.2730. [DOI] [PubMed] [Google Scholar]
  15. Goldanskii V. I., Krupyanskii Y. F. Protein and protein-bound water dynamics studied by Rayleigh scattering of Mössbauer radiation (RSMR). Q Rev Biophys. 1989 Feb;22(1):39–92. doi: 10.1017/s003358350000336x. [DOI] [PubMed] [Google Scholar]
  16. Jiang J. S., Brünger A. T. Protein hydration observed by X-ray diffraction. Solvation properties of penicillopepsin and neuraminidase crystal structures. J Mol Biol. 1994 Oct 14;243(1):100–115. doi: 10.1006/jmbi.1994.1633. [DOI] [PubMed] [Google Scholar]
  17. Lehnert U., Réat V., Weik M., Zaccaï G., Pfister C. Thermal motions in bacteriorhodopsin at different hydration levels studied by neutron scattering: correlation with kinetics and light-induced conformational changes. Biophys J. 1998 Oct;75(4):1945–1952. doi: 10.1016/S0006-3495(98)77635-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lichtenegger H., Doster W., Kleinert T., Birk A., Sepiol B., Vogl G. Heme-solvent coupling: a Mössbauer study of myoglobin in sucrose. Biophys J. 1999 Jan;76(1 Pt 1):414–422. doi: 10.1016/S0006-3495(99)77208-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lung N. P., Thompson J. P., Kollias G. V., Jr, Klein P. A. Development of monoclonal antibodies for measurement of immunoglobulin G antibody responses in blue and gold macaws (Ara ararauna). Am J Vet Res. 1996 Aug;57(8):1157–1161. [PubMed] [Google Scholar]
  20. Meyer E. Internal water molecules and H-bonding in biological macromolecules: a review of structural features with functional implications. Protein Sci. 1992 Dec;1(12):1543–1562. doi: 10.1002/pro.5560011203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Middendorf H. D. Biophysical applications of quasi-elastic and inelastic neutron scattering. Annu Rev Biophys Bioeng. 1984;13:425–451. doi: 10.1146/annurev.bb.13.060184.002233. [DOI] [PubMed] [Google Scholar]
  22. Otting G., Liepinsh E., Wüthrich K. Protein hydration in aqueous solution. Science. 1991 Nov 15;254(5034):974–980. doi: 10.1126/science.1948083. [DOI] [PubMed] [Google Scholar]
  23. Phillips G. N., Jr, Pettitt B. M. Structure and dynamics of the water around myoglobin. Protein Sci. 1995 Feb;4(2):149–158. doi: 10.1002/pro.5560040202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rasmussen B. F., Stock A. M., Ringe D., Petsko G. A. Crystalline ribonuclease A loses function below the dynamical transition at 220 K. Nature. 1992 Jun 4;357(6377):423–424. doi: 10.1038/357423a0. [DOI] [PubMed] [Google Scholar]
  25. Rupley J. A., Careri G. Protein hydration and function. Adv Protein Chem. 1991;41:37–172. doi: 10.1016/s0065-3233(08)60197-7. [DOI] [PubMed] [Google Scholar]
  26. Steinhoff H. J., Kramm B., Hess G., Owerdieck C., Redhardt A. Rotational and translational water diffusion in the hemoglobin hydration shell: dielectric and proton nuclear relaxation measurements. Biophys J. 1993 Oct;65(4):1486–1495. doi: 10.1016/S0006-3495(93)81217-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Teeter M. M. Water-protein interactions: theory and experiment. Annu Rev Biophys Biophys Chem. 1991;20:577–600. doi: 10.1146/annurev.bb.20.060191.003045. [DOI] [PubMed] [Google Scholar]
  28. Tilton R. F., Jr, Dewan J. C., Petsko G. A. Effects of temperature on protein structure and dynamics: X-ray crystallographic studies of the protein ribonuclease-A at nine different temperatures from 98 to 320 K. Biochemistry. 1992 Mar 10;31(9):2469–2481. doi: 10.1021/bi00124a006. [DOI] [PubMed] [Google Scholar]
  29. Vitkup D., Ringe D., Petsko G. A., Karplus M. Solvent mobility and the protein 'glass' transition. Nat Struct Biol. 2000 Jan;7(1):34–38. doi: 10.1038/71231. [DOI] [PubMed] [Google Scholar]
  30. Williams M. A., Goodfellow J. M., Thornton J. M. Buried waters and internal cavities in monomeric proteins. Protein Sci. 1994 Aug;3(8):1224–1235. doi: 10.1002/pro.5560030808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wlodawer A. Neutron diffraction of crystalline proteins. Prog Biophys Mol Biol. 1982;40(1-2):115–159. doi: 10.1016/0079-6107(82)90012-8. [DOI] [PubMed] [Google Scholar]
  32. Wlodawer A., Svensson L. A., Sjölin L., Gilliland G. L. Structure of phosphate-free ribonuclease A refined at 1.26 A. Biochemistry. 1988 Apr 19;27(8):2705–2717. doi: 10.1021/bi00408a010. [DOI] [PubMed] [Google Scholar]

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