Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1999 Jan;76(1 Pt 1):164–175. doi: 10.1016/S0006-3495(99)77186-9

Monte Carlo simulations of beta-hairpin folding at constant temperature.

S S Sung 1
PMCID: PMC1302508  PMID: 9876131

Abstract

Monte Carlo simulations were applied to beta-hairpin folding of a valine-based peptide. Two valine residues in the middle of the peptide were substituted with glycine, to serve as turn residues. Unlike lattice model simulations, structure prediction methods, and unfolding simulations, our simulations used an atom-based model, constant temperature (274 K), and non-beta-hairpin initial conformations. Based on the concept of solvent reference, the effective energy function simplified the solvent calculation and overcame the multiple minima problem. Driven by the hydrophobic interaction, the peptide first folded into a compact U-shaped conformation with a central turn, in analogy to the initial collapse with simultaneous nucleation in protein folding. The peptide units in the U-shaped conformation then reoriented, gradually forming hydrogen bonds in the beta-hairpin pattern from the beta-turn to the ends of the strands. With the same energy function, an alanine-based peptide folded into helix-dominated structures. The basic structure types (alpha-helix or beta-hairpin) that formed during the simulations depended upon the amino acid sequence. Compared with helix, beta-hairpin folding is driven mainly by the hydrophobic interaction. Hydrogen bonding is necessary to maintain the ordered secondary structure.

Full Text

The Full Text of this article is available as a PDF (178.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blanco F. J., Rivas G., Serrano L. A short linear peptide that folds into a native stable beta-hairpin in aqueous solution. Nat Struct Biol. 1994 Sep;1(9):584–590. doi: 10.1038/nsb0994-584. [DOI] [PubMed] [Google Scholar]
  2. Bryngelson J. D., Wolynes P. G. Spin glasses and the statistical mechanics of protein folding. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7524–7528. doi: 10.1073/pnas.84.21.7524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chakrabartty A., Kortemme T., Baldwin R. L. Helix propensities of the amino acids measured in alanine-based peptides without helix-stabilizing side-chain interactions. Protein Sci. 1994 May;3(5):843–852. doi: 10.1002/pro.5560030514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chandler D., Weeks J. D., Andersen H. C. Van der waals picture of liquids, solids, and phase transformations. Science. 1983 May 20;220(4599):787–794. doi: 10.1126/science.220.4599.787. [DOI] [PubMed] [Google Scholar]
  5. Chothia C. Hydrophobic bonding and accessible surface area in proteins. Nature. 1974 Mar 22;248(446):338–339. doi: 10.1038/248338a0. [DOI] [PubMed] [Google Scholar]
  6. Chou P. Y., Fasman G. D. Conformational parameters for amino acids in helical, beta-sheet, and random coil regions calculated from proteins. Biochemistry. 1974 Jan 15;13(2):211–222. doi: 10.1021/bi00699a001. [DOI] [PubMed] [Google Scholar]
  7. Chou P. Y., Fasman G. D. Structural and functional role of leucine residues in proteins. J Mol Biol. 1973 Mar 5;74(3):263–281. doi: 10.1016/0022-2836(73)90372-0. [DOI] [PubMed] [Google Scholar]
  8. Colonna-Cesari F., Sander C. Excluded volume approximation to protein-solvent interaction. The solvent contact model. Biophys J. 1990 May;57(5):1103–1107. doi: 10.1016/S0006-3495(90)82630-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Daggett V., Kollman P. A., Kuntz I. D. Molecular dynamics simulations of small peptides: dependence on dielectric model and pH. Biopolymers. 1991 Feb 15;31(3):285–304. doi: 10.1002/bip.360310304. [DOI] [PubMed] [Google Scholar]
  10. Daggett V., Levitt M. Molecular dynamics simulations of helix denaturation. J Mol Biol. 1992 Feb 20;223(4):1121–1138. doi: 10.1016/0022-2836(92)90264-k. [DOI] [PubMed] [Google Scholar]
  11. Daura X., Jaun B., Seebach D., van Gunsteren W. F., Mark A. E. Reversible peptide folding in solution by molecular dynamics simulation. J Mol Biol. 1998 Jul 31;280(5):925–932. doi: 10.1006/jmbi.1998.1885. [DOI] [PubMed] [Google Scholar]
  12. Dill K. A., Bromberg S., Yue K., Fiebig K. M., Yee D. P., Thomas P. D., Chan H. S. Principles of protein folding--a perspective from simple exact models. Protein Sci. 1995 Apr;4(4):561–602. doi: 10.1002/pro.5560040401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dill K. A. Theory for the folding and stability of globular proteins. Biochemistry. 1985 Mar 12;24(6):1501–1509. doi: 10.1021/bi00327a032. [DOI] [PubMed] [Google Scholar]
  14. Eisenberg D., McLachlan A. D. Solvation energy in protein folding and binding. Nature. 1986 Jan 16;319(6050):199–203. doi: 10.1038/319199a0. [DOI] [PubMed] [Google Scholar]
  15. Finkelstein A. V. Can protein unfolding simulate protein folding? Protein Eng. 1997 Aug;10(8):843–845. doi: 10.1093/protein/10.8.843. [DOI] [PubMed] [Google Scholar]
  16. Gilson M. K., Honig B. The inclusion of electrostatic hydration energies in molecular mechanics calculations. J Comput Aided Mol Des. 1991 Feb;5(1):5–20. doi: 10.1007/BF00173467. [DOI] [PubMed] [Google Scholar]
  17. Goldstein R. A., Luthey-Schulten Z. A., Wolynes P. G. Optimal protein-folding codes from spin-glass theory. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4918–4922. doi: 10.1073/pnas.89.11.4918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kabsch W., Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983 Dec;22(12):2577–2637. doi: 10.1002/bip.360221211. [DOI] [PubMed] [Google Scholar]
  19. Kortemme T., Ramírez-Alvarado M., Serrano L. Design of a 20-amino acid, three-stranded beta-sheet protein. Science. 1998 Jul 10;281(5374):253–256. doi: 10.1126/science.281.5374.253. [DOI] [PubMed] [Google Scholar]
  20. Kurochkina N., Lee B. Hydrophobic potential by pairwise surface area sum. Protein Eng. 1995 May;8(5):437–442. doi: 10.1093/protein/8.5.437. [DOI] [PubMed] [Google Scholar]
  21. Lee B., Richards F. M. The interpretation of protein structures: estimation of static accessibility. J Mol Biol. 1971 Feb 14;55(3):379–400. doi: 10.1016/0022-2836(71)90324-x. [DOI] [PubMed] [Google Scholar]
  22. Okamoto Y., Fukugita M., Nakazawa T., Kawai H. Alpha-helix folding by Monte Carlo simulated annealing in isolated C-peptide of ribonuclease A. Protein Eng. 1991 Aug;4(6):639–647. doi: 10.1093/protein/4.6.639. [DOI] [PubMed] [Google Scholar]
  23. Ooi T., Oobatake M. Prediction of the thermodynamics of protein unfolding: the helix-coil transition of poly(L-alanine). Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2859–2863. doi: 10.1073/pnas.88.7.2859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ramírez-Alvarado M., Blanco F. J., Serrano L. De novo design and structural analysis of a model beta-hairpin peptide system. Nat Struct Biol. 1996 Jul;3(7):604–612. doi: 10.1038/nsb0796-604. [DOI] [PubMed] [Google Scholar]
  25. Ripoll D. R., Scheraga H. A. On the multiple-minima problem in the conformational analysis of polypeptides. II. An electrostatically driven Monte Carlo method--tests on poly(L-alanine). Biopolymers. 1988 Aug;27(8):1283–1303. doi: 10.1002/bip.360270808. [DOI] [PubMed] [Google Scholar]
  26. Shakhnovich E. I., Gutin A. M. Influence of point mutations on protein structure: probability of a neutral mutation. J Theor Biol. 1991 Apr 21;149(4):537–546. doi: 10.1016/s0022-5193(05)80097-9. [DOI] [PubMed] [Google Scholar]
  27. Sharp K. A., Nicholls A., Friedman R., Honig B. Extracting hydrophobic free energies from experimental data: relationship to protein folding and theoretical models. Biochemistry. 1991 Oct 8;30(40):9686–9697. doi: 10.1021/bi00104a017. [DOI] [PubMed] [Google Scholar]
  28. Skolnick J., Kolinski A. Simulations of the folding of a globular protein. Science. 1990 Nov 23;250(4984):1121–1125. doi: 10.1126/science.250.4984.1121. [DOI] [PubMed] [Google Scholar]
  29. Sung S. S. Folding simulations of alanine-based peptides with lysine residues. Biophys J. 1995 Mar;68(3):826–834. doi: 10.1016/S0006-3495(95)80259-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sung S. S. Helix folding simulations with various initial conformations. Biophys J. 1994 Jun;66(6):1796–1803. doi: 10.1016/S0006-3495(94)80973-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sung S. S., Wu X. W. Molecular dynamics simulations of synthetic peptide folding. Proteins. 1996 Jun;25(2):202–214. doi: 10.1002/(SICI)1097-0134(199606)25:2<202::AID-PROT6>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
  32. Taketomi H., Ueda Y., Gō N. Studies on protein folding, unfolding and fluctuations by computer simulation. I. The effect of specific amino acid sequence represented by specific inter-unit interactions. Int J Pept Protein Res. 1975;7(6):445–459. [PubMed] [Google Scholar]
  33. Yang A. S., Honig B. Free energy determinants of secondary structure formation: I. alpha-Helices. J Mol Biol. 1995 Sep 22;252(3):351–365. doi: 10.1006/jmbi.1995.0502. [DOI] [PubMed] [Google Scholar]
  34. de Alba E., Blanco F. J., Jiménez M. A., Rico M., Nieto J. L. Interactions responsible for the pH dependence of the beta-hairpin conformational population formed by a designed linear peptide. Eur J Biochem. 1995 Oct 1;233(1):283–292. doi: 10.1111/j.1432-1033.1995.283_1.x. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES