Skip to main content
SpringerLink
Log in

Stability and fluctuations of amide hydrogen bonds in a bacterial cytochrome c: a molecular dynamics study

  • Original Article
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

Molecular dynamics (MD) simulations on a bacterial cytochrome c were performed to investigate the lifetime and fluctuations of backbone hydrogen bonds and to correlate these data with protection factors for hydrogen exchange measured by NMR spectroscopy (Bartalesi et al. in Biochemistry, 42:10923–10930, 2003). The MD simulations provide a consistent pattern in that long lifetimes of hydrogen bonds go along with small amplitude fluctuations. In agreement with experiments, differences in stability were found with a rather flexible N-terminal segment as compared with a more rigid C-terminal part. Protection factors of backbone hydrogen exchange correlate strongly with the number of contacts but also with hydrogen-bond occupancy, hydrogen-bond survival times, as well as the inverse of fluctuations of backbone atoms and hydrogen-bond lengths derived from MD simulation data. We observed a conformational transition in the C-terminal loop, and significant motion in the N-terminal loop, which can be interpreted as being the structural units involved in the onset of the protein unfolding process in agreement with experimental evidence on mitochondrial cytochrome c.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

Bcytc:

Bacterial cytochrome c

MC:

Monte Carlo

MD:

Molecular dynamics

N c n :

Number of residues which are in contact with residue n

N h n :

Number of backbone (N–H) hydrogen bonds involving residue n

PDB:

Protein Data Bank

PFE:

Protection factor elements

Q(occupancy):

Hydrogen-bond occupancy

RMS:

Root mean square

RMSF:

RMS fluctuations

RMSF−1(backbone):

Inverse of the backbone atom RMSF

RMSF−1(N–O):

Inverse of the N–O atom-pair distance (hydrogen-bond length) RMSF

References

  1. Hoang L, Bedard S, Krishna MMG, Lin Y, Englander SW (2002) Proc Natl Acad Sci USA 99:12173–12178

    Article  PubMed  CAS  Google Scholar 

  2. Li R, Woodward C (1999) Protein Sci 8:1571–1591

    Article  PubMed  CAS  Google Scholar 

  3. Milne JS, Mayne L, Roder H, Wand AJ, Englander SW (1998) Protein Sci 7:739–745

    Article  PubMed  CAS  Google Scholar 

  4. Kim KS, Fuchs JA, Woodward CK (1993) Biochemistry 32:9600–9608

    Article  PubMed  CAS  Google Scholar 

  5. Kiefhaber T, Baldwin RL (1995) Proc Natl Acad Sci USA 92:2657–2661

    Article  PubMed  CAS  Google Scholar 

  6. Bai YW, Sosnick TR, Mayne L, Englander SW (1995) Science 269:192–197

    Article  PubMed  CAS  Google Scholar 

  7. Chamberlain AK, Handel TM, Marqusee S (1996) Nat Struct Biol 3:782–787

    Article  PubMed  CAS  Google Scholar 

  8. Fuentes EJ, Wand AJ (1998) Biochemistry 37:9877–9883

    Article  PubMed  CAS  Google Scholar 

  9. Feng H, Zhou Z, Bai Y (2005) Proc Natl Acad Sci USA 102:5026–5031

    Article  PubMed  CAS  Google Scholar 

  10. Krishna MMG, Lin Y, Rumbley JN, Englander SW (2003) J Mol Biol 331:29–36

    Article  PubMed  CAS  Google Scholar 

  11. Bartalesi I, Rosato A, Zhang W (2003) Biochemistry 42:10923–10930

    Article  PubMed  CAS  Google Scholar 

  12. Ferraro DM, Robertson AD (2004) Biochemistry 43:587–594

    Article  PubMed  CAS  Google Scholar 

  13. Chamberlain AK, Marqusee S (1998) Biochemistry 37:1736–1742

    Article  PubMed  CAS  Google Scholar 

  14. Alonso DOV, Daggett V (1995) J Mol Biol 247:501–520

    Article  PubMed  CAS  Google Scholar 

  15. Garcia AE, Hummer G (1999) Proteins 36:175–191

    Article  PubMed  CAS  Google Scholar 

  16. Brooks CL III (1992) J Mol Biol 227:375–980

    Article  PubMed  CAS  Google Scholar 

  17. Chothia C, Lesk AM (1985) J Mol Biol 182:151–158

    Article  PubMed  CAS  Google Scholar 

  18. Maity H, Maity M, Englander SW (2004) J Mol Biol 343:223–233

    Article  PubMed  CAS  Google Scholar 

  19. Banci L, Bertini I, Ciurli S, Dikiy A, Rosato A, Sciara G, Thompsett AR (2002) Chembiochem 3:299–310

    Article  PubMed  CAS  Google Scholar 

  20. Benini S, González A, Rypniewski WR, Wilson KS, Beeumen JJV, Ciurli S (2000) Biochemistry 39:13115–13126

    Article  PubMed  CAS  Google Scholar 

  21. Vandenberghe IHM, Guisez Y, Ciurli S, Benini S, Beeumen JJV (1999) Biochem Biophys Res Commun 264:380–387

    Article  PubMed  CAS  Google Scholar 

  22. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) J Comp Chem 4:187–217

    Article  CAS  Google Scholar 

  23. A D MacKerell J, Bashford D, Bellott M, R L Dunbrack J, Evanseck J, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, W E Reiher I, Roux B, Schlenkrich M, Smith J, Stote R, Straub J, Watanabe M, Wiorkiewicz-Kuczera J, Yin D, Karplus M (1998) J Phys Chem B 102:3586–3616

    Article  CAS  Google Scholar 

  24. Voigt P, Knapp EW (2003) J Biol Chem 278:51293–51301

    Article  CAS  Google Scholar 

  25. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein M (1983) J Chem Phys 79:926–935

    Article  CAS  Google Scholar 

  26. Ryckaert JP, Ciccotti G, Berendsen HJC (1977) J Comput Phys 23:327–341

    Article  CAS  Google Scholar 

  27. Nose S (1984) J Chem Phys 81:511–519

    Article  CAS  Google Scholar 

  28. Hoover WG (1985) Phys Rev A 31:1695–1697

    Article  PubMed  Google Scholar 

  29. Kabsch W (1976) Acta Cryst A32:922–923

    Google Scholar 

  30. Fersht AR (1999) Structure and mechanism in protein science. W. H. Freeman & Co., New York

    Google Scholar 

  31. Vendruscolo M, Paci E, Dobson CM, Karplus M (2003) J Am Chem Soc 125:15686–15687

    Article  PubMed  CAS  Google Scholar 

  32. Parak F, Knapp EW (1984) Proc Natl Acad Sci USA Biol Sci 81:7088–7092

    Article  CAS  Google Scholar 

  33. Muegge I, Knapp EW (1995) J Phys Chem 99:1371–1374

    Article  CAS  Google Scholar 

  34. Hoang L, Maity H, Krishna MMG, Lin Y, Englander SW (2003) J Mol Biol 331:37–43

    Article  PubMed  CAS  Google Scholar 

  35. Bartalesi I, Bertini I, Rosato A (2003) Biochemistry 42:739–745

    Article  PubMed  CAS  Google Scholar 

  36. Morelli X, Guerlesquin F (1999) FEBS Lett 460:77–80

    Article  PubMed  CAS  Google Scholar 

  37. Hunte C, Solmaz S, Lange C (2002) Biochim Biophys Acta 1555:21–28

    Article  PubMed  CAS  Google Scholar 

  38. Maity H, Lim WK, Rumbley JN, Englander SW (2003) Proteins Sci 12:153–160

    Article  CAS  Google Scholar 

  39. Englander SW, Mayne L (1992) Annu Rev Biophys Biomol Struct 21:243

    Article  PubMed  CAS  Google Scholar 

  40. Morra G, Hodoscek M, Knapp EW (2003) Proteins 53:597–606

    Article  PubMed  CAS  Google Scholar 

  41. Kraulis PJ (1991) J Appl Cryst 24:946–950

    Article  Google Scholar 

Download references

Acknowledgements

We would like to thank Franz X. Schmidt and Hiroshi Ishikita for useful discussions. We also thank Antonio Rosato, who kindly provided us with experimental data in electronic form. This project was supported by the Deutsche Forschungsgemeinschaft SFB 498, Project A5, Forschergruppe Project KN 329/5-1/5-2, GRK 80/2, GRK 268/2, GRK 788/1.

Author information

Authors and Affiliations

  1. Department of Biology, Chemistry, Pharmacy, Institute of Chemistry and Biochemistry, Free University of Berlin, Takustrasse 6, 14195, Berlin, Germany

    Gernot Kieseritzky, Giulia Morra & Ernst-Walter Knapp

Authors
  1. Gernot Kieseritzky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giulia Morra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ernst-Walter Knapp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ernst-Walter Knapp.

Additional information

Gernot Kieseritzky and Giulia Morra both contributed equally to this work.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kieseritzky, G., Morra, G. & Knapp, EW. Stability and fluctuations of amide hydrogen bonds in a bacterial cytochrome c: a molecular dynamics study. J Biol Inorg Chem 11, 26–40 (2006). https://doi.org/10.1007/s00775-005-0041-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-005-0041-1

Keywords

Search

Navigation