Skip to main content
SpringerLink
Log in

Conformational Energy Calculations on Polypeptides and Proteins

  • Chapter
Molecular Aspects of Biotechnology: Computational Models and Theories

Part of the book series: NATO ASI Series ((ASIC,volume 368))

  • 91 Accesses

Abstract

Empirical conformational energy functions are used to try to compute the three-dimensional structures of polypeptides and proteins. The conformational energy surfaces of such molecules have many local minima, and conventional energy minimization procedures reach only a local minimum (near the starting point of the optimization algorithm) instead of the global minimum (the multiple-minima problem). Several procedures have been developed to surmount this problem. A summary is given here of five of these methods, (i) build-up, (ii) Monte Carlo-plus- minimization (MCM), (iii) relaxation of dimensionality, (iv) pattern-recognition-based importance-sampling minimization (PRISM), and (v) the diffusion equation method which smoothes out the potential surface, leaving only the potential well containing the global minimum. These and other procedures have been applied to a variety of polypeptide structural problems. These include the computation of the structures of open-chain and cyclic peptides, fibrous proteins and globular proteins. Present efforts are being devoted to scaling up these procedures from small polypeptides to proteins, to try to compute the three-dimensional structure of a protein from its amino sequence.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anfinsen, C. B., Haber, E., Sela, M. and White, F. H., Jr. (1961) ‘The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain’, Proc. Natl. Acad. Sci., U.S.A. 47, 1309–1314.

    Article  CAS  Google Scholar 

  2. Scheraga, H. A. (1991) ‘Experimental and theoretical aspects of protein conformation’, in Theoretical Biochemistry and Molecular Biophysics, Vol. 2: Proteins, Ed. D. L. Beveridge and R. Lavery, Adenine Press, Guilderland, N.Y., p. 231–237.

    Google Scholar 

  3. Vásquez, M. and Scheraga, H. A. (1988) ‘Calculation of protein conformation by the build-up procedure. Application to bovine pancreatic trypsin inhibitor using limited simulated nuclear magnetic resonance data’, J. Biomolecular Structure & Dynamics 5, 705–755.

    Google Scholar 

  4. Vásquez, M. and Scheraga, H. A. (1988) ‘Variable-target-function and build-up procedures for the calculation of protein conformation. Application to bovine pancreatic trypsin inhibitor using limited simulated nuclear magnetic resonance data’, J. Biomolecular Structure & Dynamics 5, 757–784.

    Google Scholar 

  5. Simon, I., Glasser, L. and Scheraga, H. A. (1991) ‘Calculation of protein conformation as an assembly of stable overlapping segments: Application of bovine pancreatic trypsin inhibitor’, Proc. Natl. Acad. Sci., USA 88, 3661–3665.

    Article  CAS  Google Scholar 

  6. Li, Z. and Scheraga, H. A. (1987) ‘Monte Carlo-minimization approach to the multiple-minima problem in protein folding’, Proc. Natl. Acad. Sci., U.S.A. 84, 6611–6615.

    Article  CAS  Google Scholar 

  7. Li, Z. and Scheraga, H. A. (1988) ‘Structure and free energy of complex thermodynamic systems’, J. Molec. Str. (Theochem). 179, 333–352.

    Article  Google Scholar 

  8. Purisima, E. O. and Scheraga, H. A. (1986) ‘An approach to the multiple-minima problem by relaxing dimensionality’, Proc. Natl. Acad. Sci., U.S.A. 83, 2782–2786.

    Article  CAS  Google Scholar 

  9. Purisima, E. O. and Scheraga, H. A. (1987) ‘An approach to the multiple-minima problem in protein folding by relaxing dimensionality. Tests on enkephalin’, J. Mol. Biol. 196, 697–709.

    Article  CAS  Google Scholar 

  10. Lambert, M. H. and Scheraga, H. A. (1989) ‘Pattern recognition in the prediction of protein structure. I. Tripeptide conformational probabilities calculated from the amino acid sequence’, J. Comput. Chem. 10, 770–797.

    Article  CAS  Google Scholar 

  11. Lambert, M. H. and Scheraga, H. A. (1989) ‘Pattern recognition in the prediction of protein structure. II. Chain conformation from a probability-directed search procedure’, J. Comput. Chem. 10, 798–816.

    Article  CAS  Google Scholar 

  12. Lambert, M. H. and Scheraga, H. A. (1989) ‘Pattern recognition in the prediction of protein structure. III. An importance-sampling minimization procedure’, J. Comput. Chem. 10, 817–831.

    Article  CAS  Google Scholar 

  13. Piela, L., Kostrowicki, J. and Scheraga, H. A. (1989) ‘The multiple-minima problem in the conformational analysis of molecules. Deformation of the potential energy hypersurface by the diffusion equation method’, J. Phys. Chem. 93, 3339–3346.

    Article  CAS  Google Scholar 

  14. Kostrowicki, J., Piela, L., Cherayil, B. J. and Scheraga, H. A. (1991) ‘Performance of the diffusion equation method in searches for optimum structures of clusters of Lennard-Jones atoms’, J. Phys. Chem. 95, 4113–4119.

    Article  CAS  Google Scholar 

  15. Kostrowicki, J. and Scheraga, H. A. (1991) work in progress.

    Google Scholar 

  16. Vásquez, M. and Scheraga, H. A. (1985) ‘Use of buildup and energy-minimization procedures to compute low-energy structures of the backbone of enkephalin’, Biopolymers 24, 1437–1447.

    Article  Google Scholar 

  17. Glasser, L. and Scheraga, H. A. (1988) ‘Calculations on crystal packing of a flexible molecule, Leu-enkephalin’, J. Mol. Biol. 199, 513–524.

    Article  CAS  Google Scholar 

  18. Dygert, M., Go, N. and Scheraga, H. A. (1975) ‘Use of a symmetry condition to compute the conformation of gramicidin S’, Macromolecules 8, 750–761.

    Article  CAS  Google Scholar 

  19. Miller, M. H. and Scheraga, H. A. (1976) ‘Calculation of the structures of collagen models. Role of interchain interactions in determining the triple-helical coiled-coil conformation. I. Poly(glycyl-prolyl-prolyl)’, J. Polymer Sci.: Polymer Symposia, No 54, p. 171–200.

    Google Scholar 

  20. Gō, N. and Scheraga, H. A. (1973) ‘Ring closure in chain molecules with Cn, I or S2n symmetry’, Macromolecules 6, 273–281.

    Article  Google Scholar 

  21. Mirau, P. A. and Bovey, F. A. (1990) ‘2D and 3D NMR studies of polypeptide structure and function’, Abstracts 199th April Amer. Chem. Soc. Meeting, Boston, POLY 58.

    Google Scholar 

  22. Okuyama, K., Tanaka, N., Ashida, T. and Kakudo, M. (1976) ‘Structure analysis of a collagen model polypeptide, (Pro-Pro-GlY) 10’, Bull. Chem. Soc. Japan 49, 1805–1810.

    Article  CAS  Google Scholar 

  23. Gibson, K. D., Chin, S., Pincus, M. R., Clementi, E. and Scheraga, H. A. (1986) ‘Parallelism in conformational energy calculations on proteins’, in “Lecture Notes in Chemistry,” Vol. 44, “Super-computer Simulations in Chemistry,” ed. M. Dupuis, Springer-Verlag, Berlin, 1986, p. 198–213.

    Google Scholar 

  24. Simon, I. (1985) ‘Investigation of protein refolding: A special feature of native structure responsible for refolding ability’, J. Theor. Biol. 113, 703–710.

    Article  CAS  Google Scholar 

  25. Vonderviszt, F., Matrai, G. and Simon, I. (1986) ‘Characteristic sequential residue environment of amino acids in proteins’, Int. J. Peptide Protein Res. 27, 483–492.

    Article  CAS  Google Scholar 

  26. Vonderviszt, F. and Simon, I. (1986) ‘A possible way for prediction of domain boundaries in globular proteins from amino acid sequence’, Biochem. Biophys. Res. Commun. 139, 11–17.

    Article  CAS  Google Scholar 

  27. Cserzo, M. and Simon, I. (1989) ‘Regularities in the primary structure of proteins’, Int. J. Peptide Protein Res. 34, 184–195.

    Article  CAS  Google Scholar 

  28. Tudos, E., Cserzo, M. and Simon, I. (1990) ‘Predicting isomorphic residue replacements for protein design’, Int. J. Peptide Protein Res. 36, 236–239.

    Article  CAS  Google Scholar 

  29. Zimmerman, S. S., Pottle, M. S., Némethy, G. and Scheraga, H. A. (1977) ‘Conformational analysis of the twenty naturally occurring amino acid residues using ECEPP’, Macromolecules 10, 1–9.

    Article  CAS  Google Scholar 

  30. Burgess, A. W. and Scheraga, H. A. (1975) ‘Assessment of some problems associated with prediction of the three-dimensional structure of a protein from its amino-acid sequence’, Proc. Natl. Acad. Sci., U.S. 72, 1221–1225.

    Article  CAS  Google Scholar 

  31. Metropolis, N., Rosenbluth, A. W., Rosenbluth, M. N., Teller, A. H. and Teller, E. (1953) ‘Equation of state calculations by fast computing machines’, J. Chem. Phys. 21, 1087–1092.

    Article  CAS  Google Scholar 

  32. Momany, F. A., McGuire, R. F., Burgess, A. W. and Scheraga, H. A. (1975) ‘Energy parameters in polypeptides. VII. Geometric parameters, partial atomic charges, nonbonded interactions, hydrogen bond interactions, and intrinsic torsional potentials for the naturally occurring amino acids’, J. Phys. Chem. 79, 2361–2381.

    Article  CAS  Google Scholar 

  33. Némethy, G., Pottle, M. S. and Scheraga, H. A. (1983) ‘Energy parameters in polypeptides. 9. Updating of geometrical parameters, nonbonded interactions, and hydrogen bond interactions for the naturally occurring amino acids’, J. Phys. Chem. 87, 1883–1887.

    Article  Google Scholar 

  34. Sippl, M. J., Némethy, G. and Scheraga, H. A. (1984) ‘Intermolecular potentials from crystal data. 6. Determination of empirical potentials for O-H···O=C hydrogen bonds from packing configurations’, J. Phys. Chem. 88, 6231–6233.

    Article  CAS  Google Scholar 

  35. Nayeem, A., Vila, J. and Scheraga, H. A. (1991) ‘A comparative study of the simulated-annealing and Monte Carlo-with-minimization approaches to the minimum-energy structures of polypeptides: [Met]-Enkephalin’, J. Comput. Chem. 12, 594–605.

    Article  CAS  Google Scholar 

  36. Kirkpatrick, S., Gelatt, C. D., Jr. and Vecchi, M. P. (1983) ‘Optimization by simulated annealing’, Science 220, 671–680.

    Article  CAS  Google Scholar 

  37. Vanderbilt, D. and Louie, S. G. (1984) ‘A Monte Carlo simulated annealing approach to optimization over continuous variables’, J. Comput. Phys. 56, 259–271.

    Article  Google Scholar 

  38. Crippen, G. M. (1982) ‘Conformational analysis by energy embedding’, J. Comput. Chem. 3, 471–476.

    Article  CAS  Google Scholar 

  39. Crippen, G. M. (1984) ‘Conformational Analysis by scaled energy embedding’, J. Comput. Chem. 5, 548–554.

    Article  CAS  Google Scholar 

  40. Blumenthal, L. M. (1970) “Theory and Applications of Distance Geometry”, Chelsea, New York, 97–99.

    Google Scholar 

  41. Kidera, A., Konishi, Y., Oka, M., Ooi, T. and Scheraga, H. A. (1985) ‘Statistical analysis of the physical properties of the 20 naturally occurring amino acids’, J. Protein Chem. 4, 23–55.

    Article  CAS  Google Scholar 

  42. Blundell, T. L., Pitts, J. E., Tickle, I. J., Wood, S. P. and Wu, C. W. (1981) ‘X-ray analysis (1.4-Å resolution) of avian pancreatic polypeptide: Small globular protein hormone’, Proc. Natl. Acad. Sci., U.S.A. 78, 4175–4179.

    Article  CAS  Google Scholar 

  43. Glover, I., Haneef, I., Pitts, J., Wood, S., Moss, D., Tickle, I. and Blundell, T. (1983) ‘Conformational flexibility in a small globular hormone: X-ray analysis of avian pancreatic polypeptide at 0.98-Å resolution’, Biopolymers 22, 293–304.

    Article  CAS  Google Scholar 

  44. Kostrowicki, J. and Piela, L. (1991) ‘Diffusion equation method of global minimization: Performance for standard test functions’, J. Optimization Theory and Applications 69, 269–284.

    Article  Google Scholar 

  45. Mackay, A. L. (1962) ‘A dense non-crystallographic packing of equal spheres’, Acta Cryst. 15, 916–918.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Baker Laboratory of Chemistry, Cornell University, Ithaca, New York, 14853-1301, USA

    Harold A. Scheraga

Authors
  1. Harold A. Scheraga
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Chemistry, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain

    Juan Bertrán

Rights and permissions

Reprints and permissions

Copyright information

© 1992 Kluwer Academic Publishers

About this chapter

Cite this chapter

Scheraga, H.A. (1992). Conformational Energy Calculations on Polypeptides and Proteins. In: Bertrán, J. (eds) Molecular Aspects of Biotechnology: Computational Models and Theories. NATO ASI Series, vol 368. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-2538-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-2538-3_1

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-0-7923-1728-9

  • Online ISBN: 978-94-011-2538-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation