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:

Surface topography dependence of biomolecular hydrophobic hydration

Nature volume 392, pages 696–699 (1998)Cite this article

Abstract

Many biomolecules are characterized by surfaces containing extended nonpolar regions1, and the aggregation and subsequent removal of such surfaces from water is believed to play a critical role in the biomolecular assembly in cells2. A better understanding of the hydrophobic hydration of biomolecules may therefore yield new insights into intracellular assembly. Conventional views hold that the hydration shell of small hydrophobic solutes is clathrate-like, characterized by local cage-like hydrogen-bonding structures and a distinct loss in entropy2. The hydration of extended nonpolar planar surfaces, however, appears to involve structures that are orientationally inverted relative to clathrate-like hydration shells3,4, with unsatisfied hydrogen bonds that are directed towards the hydrophobic surface. Here we present computer simulations of the interaction between the polypeptide melittin and water that demonstrate that the two different hydration structures also exist near a biomolecular surface. We find that the two structures are distinguished by a substantial difference in the water–water interaction enthalpy, and that their relative contributions depend strongly on the surface topography of the melittin molecule: clathrate-like structures dominate near convex surface patches, whereas the hydration shell near flat surfaces fluctuates between clathrate-like and less-ordered or inverted structures. The strong influence of surface topography on the structure and free energy of hydrophobic hydration is likely to hold in general, and will be particularly important for the many biomolecules whose surfaces contain convex patches, deep or shallow concave grooves and roughly planar areas5.

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: Stereographic image of the hydrophobic surface of the melittin dimer9; this is completely buried on tetramerization.
Figure 2: Statistical distribution of the orientation of proximal water molecules in ten consecutive time segments (t1 to t10).
Figure 3: Comparison of proximal solvent energetics.

Similar content being viewed by others

References

  1. Teeter, M. M. Water–protein interactions: Theory and experiment. Annu. Rev. Biophys. Biophys. Chem. 20, 577–600 (1991).

    Article  CAS  Google Scholar 

  2. Blokzijl, W. & Engberts, J. B. F. N. Hydrophobic effects. Opinions and facts. Angew. Chem. Int. Edn Engl. 32, 1545–1579 (1993).

    Article  Google Scholar 

  3. Lee, C. Y., MCammon, J. A. & Rossky, P. J. The structure of liquid water at an extended hydrophobic surface. J. Chem. Phys. 80, 4448–4455 (1984).

    Article  ADS  CAS  Google Scholar 

  4. Du, Q., Freysz, E. & Shen, Y. R. Surface vibrational spectroscopic studies of hydrogen bonding and hydrophobicity. Science 264, 826–828 (1994).

    Article  ADS  CAS  Google Scholar 

  5. Kuhn, L. A. et al. The interdependence of protein surface topography and bound water molecules revealed by surface accessibility and fractal density measures. J. Mol. Biol. 228, 13–22 (1992).

    Article  CAS  Google Scholar 

  6. Sharp, K. A., Nicholls, A., Fine, R. F. & Honig, B. Reconciling the magnitude of the microscopic and macroscopic hydrophobic effects. Science 252, 106–109 (1991).

    Article  ADS  CAS  Google Scholar 

  7. Sanchez-Ruiz, J. M. Molecular-size corrections to the strength of the hydrophobic effect: A critical review. Eur. Biophys. J. 24, 261–274 (1996).

    Article  CAS  Google Scholar 

  8. Dempsey, C. E. The actions of melittin on membranes. Biochim. Biophys. Acta 1031, 143–161 (1990).

    Article  CAS  Google Scholar 

  9. Terwilliger, T. C. & Eisenberg, D. The structure of melittin. I. Structure determinations and partial refinement. J. Biol. Chem. 257, 6010–6015 (1982).

    CAS  PubMed  Google Scholar 

  10. Clarke, A. R. & Lund, P. A. in The ChaperoninsCh. 7 (ed. Ellis, R. J.) 167–212 (Academic, San Diego, 1996).

    Book  Google Scholar 

  11. Bernstein, F. C. et al. The protein data bank: A computer-based archival file for macromolecular structures. J. Biol. Chem. 112, 535–542 (1977).

    CAS  Google Scholar 

  12. Kitao, A., Hirata, F. & Go, N. The effects of solvent on the conformation and collective motions of protein: Normal mode analysis and molecular dynamics simulations of melittin in water and in vacuum. Chem. Phys. 158, 447–472 (1991).

    Article  CAS  Google Scholar 

  13. Mehrotra, P. K. & Beveridge, D. L. Structural analysis of molecular solutions based on quasi-component distribution functions. Application to [H2CO]aq at 25 °C. J. Am. Chem. Soc. 102, 4287–4294 (1980).

    Article  CAS  Google Scholar 

  14. Zichi, D. A. & Rossky, P. J. The equilibrium solvation structure for the solvent-separated hydrophobic bond. J. Chem. Phys. 83, 797–808 (1985).

    Article  ADS  CAS  Google Scholar 

  15. Rossky, P. J. & Karplus, M. Solvation. A molecular dynamics study of a dipeptide in water. J. Am. Chem. Soc. 101, 1913–1937 (1979).

    Article  CAS  Google Scholar 

  16. Pascual-Ahuir, J. L., Silla, E. & Tunon, I. GEPOL: An improved description of molecular surfaces. III. A new algorithm for the computation of the solvent-excluding surface. J. Comput. Chem. 15, 1127–1138 (1994).

    Article  CAS  Google Scholar 

  17. Freire, E., Murphy, K. P., Sanchez-Ruiz, J. M., Galiseo, M. L. & Privalov, P. L. The molecular basis of cooperativity in protein folding. Thermodynamic dissection of interdomain interactions in phosphoglycerate kinase. Biochemistry 31, 250–256 (1992).

    Article  CAS  Google Scholar 

  18. Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F. & Hermans, J. in Intermolecular Forces (ed. Pullman, B.) 331–342 (Reidel, Dordrecht, 1981).

    Book  Google Scholar 

  19. Jorgensen, W. L. & Tirado-Rives, J. The OPLS potential functions for proteins. Energy minimizations for crystals of cyclic peptides and crambin. J. Am. Chem. Soc. 110, 1657–1671 (1988).

    Article  CAS  Google Scholar 

  20. Verlet, L. Computer “experiments” on classical fluids. I. Thermodynamical properties of Lennard–Jones molecules. Phys. Rev. 159, 98–103 (1967).

    Article  ADS  CAS  Google Scholar 

  21. Ryckaert, J.-P., Ciccotti, G. & Berendsen, H. J. C. Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comput. Phys. 23, 327–341 (1977).

    Article  ADS  CAS  Google Scholar 

  22. Nicholls, A., Sharp, K. A. & Honig, B. Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins 11, 281–296 (1991).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge contributions from W. S. Sheu and T. S. Cohen in the early stages of this work. This work was supported by the NIH.

Author information

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, 78712-1167, Texas, USA

    Yuen-Kit Cheng & Peter J. Rossky

Authors
  1. Yuen-Kit Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter J. Rossky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter J. Rossky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheng, YK., Rossky, P. Surface topography dependence of biomolecular hydrophobic hydration. Nature 392, 696–699 (1998). https://doi.org/10.1038/33653

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/33653

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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