Skip to main content
SpringerLink
Log in

Conformational search by potential energy annealing: Algorithm and application to cyclosporin A

  • Research Papers
  • Published:
Journal of Computer-Aided Molecular Design Aims and scope Submit manuscript

Summary

A major problem in modelling (biological) macromolecules is the search for low-energy conformations. The complexity of a conformational search problem increases exponentially with the number of degrees of freedom which means that a systematic search can only be performed for very small structures. Here we introduce a new method (PEACS) which has a far better performance than conventional search methods.

To show the advantages of PEACS we applied it to the refinement of Cyclosporin A and compared the results with normal molecular dynamics (MD) refinement. The structures obtained with PEACS were lower in energy and agreed with the NMR parameters much better than those obtained with MD. From the results it is further clear that PEACS samples a much larger part of the available conformational space than MD does.

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

Similar content being viewed by others

References

  1. Garey, M.R. and Johnson, D.S., Computers and Intractability: A guide to the Theory of NP-Completeness, Freeman, San Francisco, 1979.

    Google Scholar 

  2. Wiberg, K.B. and Boyd, R.H., J. Am. Chem. Soc., 94 (1972) 8426.

    Google Scholar 

  3. Lipton, M. and Still, W.C., J. Comput. Chem., 9 (1988) 343.

    Google Scholar 

  4. Griewank, A.O., J. Opt. Theor. Appl., 34 (1981) 11.

    Google Scholar 

  5. A recent monograph on Molecular Dynamics and Monte Carlo techniques is: Allen, M.P. and Tildesley, D.J., Computer Simulation of Liquids, Clarendon, Oxford, 1987.

  6. Northrup, S.H. and McCammon, J.A., Biopolymers, 19 (1980) 1001.

    Google Scholar 

  7. DiNola, A., Berendsen, H.J.C. and Edholm, O., Macromolecules, 17 (1984) 2044.

    Google Scholar 

  8. Kirkpatrick, S., Gelatti, Jr., C.D. and Vecchi, M.P., Science, 220 (1983) 671.

    Google Scholar 

  9. van Gunsteren, W.F., Kaptein, R. and Zuiderweg, E.R.P., In Olson, W.K. (Ed.) Nucleic Acid Conformation and Dynamics, Proceedings of a NATO/CECAM Workshop, CECAM, Orsay, 1984, pp. 79–92.

  10. Brünger, A.T., Kuriyan, J. and Karplus, M., Science, 235 (1987) 458.

    Google Scholar 

  11. For a review see: Scheraga, H.A., Chemica Scripta, 29A (1989) 3.

    Google Scholar 

  12. Piela, L., Kostrowicki, J. and Scheraga, H.A., J. Phys. Chem., 93 (1989) 3339.

    Google Scholar 

  13. Nilges, M., Clore, G.M. and Gronenborn, A.M., FEBS Lett., 239 (1988) 129.

    Google Scholar 

  14. Crippen, G.M., J. Comput. Chem., 3 (1982) 471.

    Google Scholar 

  15. Crippen, G.M., J. Comput. Chem., 5 (1984) 548.

    Google Scholar 

  16. Purisma, E.O. and Scheraga, H.A., Proc. Natl. Acad. Sci. U.S.A., 83 (1986) 2782.

    Google Scholar 

  17. Purisma, E.O. and Scheraga, H.A., J. Mol. Biol., 196 (1987) 697.

    Google Scholar 

  18. Donnelly, R.A. and Rogers, Jr., J.W., Int. J. Quantum Chem.: Quantum Chem. Symp., 22 (1988) 507.

    Google Scholar 

  19. Cotterill, R.M.J. and Madsen, J.U., In Characterizing Complex Systems, Bohr, H. (Ed.) World Scientific, Singapore, 1990, pp. 177–191.

    Google Scholar 

  20. Lautz, J., Kessler, H., Blaney, J.M., Scheek, R.M. and van, Gunsteren, W.F., Int. J. Pept. Prot. Res., 33 (1989) 281.

    Google Scholar 

  21. Lautz, J., Kessler, H., Kaptein, R. and van, Gunsteren, W.F., J. Comput.-Aided Mol. Design, 1 (1987) 219.

    Google Scholar 

  22. Berendsen, H.J.C., Postma, J.P.M., van, Gunsteren, W.F., DiNola, A. and Haak, J.R., J. Chem. Phys., 81 (1984) 3684.

    Google Scholar 

  23. van, Gunsteren, W.F. and Berendsen, H.J.C., Groningen Molecular Simulation (GROMOS) Library Manual, Biomos, Groningen, 1987.

    Google Scholar 

  24. Åqvist, J., van, Gunsteren, W.F., Leijonmarck, M. and Tapia, O., J. Mol. Biol., 183 (1985) 461.

    Google Scholar 

  25. van, Gunsteren, W.F. and Berendsen, H.J.C., In Hermans, J. (Ed.) Molecular Dynamics and Protein Structures, Polycrystal Books Service, Western Springs, IL., 1985, pp. 5–14.

    Google Scholar 

  26. Ryckaert, J.P., Ciccotti, G.H. and Berendsen, H.J.C., J. Comput. Phys., 23 (1977) 327.

    Google Scholar 

  27. van, Gunsteren, W.F. and Berendsen, H.J.C., Mol. Phys., 34 (1977) 1311.

    Google Scholar 

  28. Loosli, H.R., Kessler, H., Oschkinat, H., Weber, H.P., Petcher, T.J. and Widmer, A., Helv. Chim. Acta, 68 (1985) 682.

    Google Scholar 

  29. Berendsen, H.J.C., van, Gunsteren, W.F., Zwinderman, H.R. and Geurtsen, R.G., Ann. N.Y. Acad. Sci., 482 (1986) 264.

    Google Scholar 

  30. Torda, A.E., Scheek, R.M. and van, Gunsteren, W.F., Chem. Phys. Lett., 157 (1989) 289.

    Google Scholar 

  31. Torda, A.E., Scheek, R.M. and van, Gunsteren, W.F., J. Mol. Biol., 214 (1990) 223.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biophysical Chemistry, Rijksuniversiteit Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands

    René C. van Schaik & Herman J. C. Berendsen

  2. Laboratorium für Physikalische Chemie, ETH-Zentrum, CH-8092, Zürich, Switzerland

    Wilfred F. van Gunsteren

Authors
  1. René C. van Schaik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wilfred F. van Gunsteren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Herman J. C. Berendsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Schaik, R.C., van Gunsteren, W.F. & Berendsen, H.J.C. Conformational search by potential energy annealing: Algorithm and application to cyclosporin A. J Computer-Aided Mol Des 6, 97–112 (1992). https://doi.org/10.1007/BF00129422

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00129422

Key words

Search

Navigation