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Journal of Computer-Aided Molecular Design

, Volume 8, Issue 3, pp 257–272 | Cite as

Shape information from a critical point analysis of calculated electron density maps: Application to DNA-drug systems

  • Laurence Leherte
  • Frank H. Allen
Research Papers

Summary

A computational method is described for mapping the volume within the DNA double helix accessible to the groove-binding antibiotic netropsin. Topological critical point analysis is used to locate maxima in electron density maps reconstructed from crystallographically determined atomic coordinates. The peaks obtained in this way are represented as ellipsoids with axes related to local curvature of the electron density function. Combining the ellipsoids produces a single electron density function which can be probed to estimate effective volumes of the interacting species. Close complementarity between host and ligand in this example shows the method to give a good representation of the electron density function at various resolutions. At the atomic level, the ellipsoid method gives results which are in close agreement with those from the conventional spherical van der Waals approach.

Key words

Molecular shape analysis Critical point analysis Electron density maps DNA-drug interactions 

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References

  1. 1.
    Connolly, M.L., J. Appl. Crystallogr., 16 (1983) 548.Google Scholar
  2. 2.
    Del, Carpio, C.A., Takahashi, Y. and Sasaki, S.-I., J. Mol. Graphics, 11 (1993) 23.Google Scholar
  3. 3.
    Santavy, M. and Kypr, J., J. Mol. Graphics, 2 (1984) 47.Google Scholar
  4. 4.
    Fortier, S., Castleden, I., Glasgow, J., Conklin, D., Walmsley, C., Leherte, L. and Allen, F.H., Acta Crystallogr., D49 (1993) 168.Google Scholar
  5. 5.
    Kennard, O. and Hunter, W.N., Angew. Chem., Int. Ed. Engl., 30 (1991) 1254.Google Scholar
  6. 6.
    Kopka, M.L. and Larsen, T.A., In Propst, C.L. and Perun, T.J. (Eds.) Nucleic Acid Targeted Drug Design, Marcel Dekker, New York, NY, 1992, pp. 302–374.Google Scholar
  7. 7.
    Saenger, W., Principles of Nucleic Acid Structure, Springer, New York, NY, 1984.Google Scholar
  8. 8.
    Wang, A.H.-J. and Teng, M.-K., In Bugg, C.E. and Ealick, S.E. (Eds.) Crystallographic and Modelling Methods in Molecular Design, Springer, New York, NY, 1990, pp. 123–150.Google Scholar
  9. 9.
    Dickerson, R.E., Kopka, M.L. and Pjura, P.E., In Guschlbauer, W. and Saenger, W. (Eds.) DNA-Ligand Interactions: From Drugs to Proteins, Plenum Press, New York, NY, 1987, pp. 45–62.Google Scholar
  10. 10.
    Lavery, R. and Pullman, B., Int. J. Quantum Chem., 20 (1981) 259.Google Scholar
  11. 11.
    Bader, R.F.W., Atoms in Molecules, Clarendon Press, Oxford, 1990.Google Scholar
  12. 12.
    Johnson, C.K., Proceedings of the American Crystallographic Association Meeting 1976, Evanston, IL, Abstr. B1.Google Scholar
  13. 13.
    Johnson, C.K., Proceedings of the American Crystallographic Association Meeting 1977, Asilomar, CA, Abstr. JQ6.Google Scholar
  14. 14.
    Johnson, C.K., ORCRIT, The Oak Ridge Critical Point Network Program, Chemistry Division, Oak Ridge National Laboratory, Oak Ridge, TN, 1977.Google Scholar
  15. 15.
    Hall, S.R. and Stewart, J.M. (Eds.) XTAL 3.0 Users Manual, Universities of Western Australia and Maryland, 1990.Google Scholar
  16. 16.
    Bernstein, F.C., Koetzle, T.F., Williams, G.J.B., Meyer, E.F., Brice, M.D., Rodgers, J.R., Kennard, O., Shimanouchi, T. and Tasumi, M., J. Mol. Biol., 112 (1978) 535.Google Scholar
  17. 17.
    Berman, H.M., Olson, W.K., Beveridge, D.L., Westbrook, J., Glebin, A., Demeny, T., Hsieh, S.-H., Srinivasan, A.R. and Schneider, B., Biophys. J., 63 (1992) 751.Google Scholar
  18. 18.
    Drew, H.R., Wing, R.M., Takano, T., Broka, C., Tanaka, S., Itakura, K. and Dickerson, R.E., Proc. Natl. Acad. Sci. USA, 78 (1981) 2179.Google Scholar
  19. 19.
    Coll, M., Aymami, J., Van der, Marel, G.A., Van, Boom, J.H., Rich, A. and Wang, A.H.-J., Biochemistry, 28 (1989) 310.Google Scholar
  20. 20.
    Kopka, M.L., Yoon, C., Goodsell, D., Pjura, P. and Dickerson, R.E., J. Mol. Biol., 183 (1985) 553.Google Scholar
  21. 21.
    Derouane, E.G., Leherte, L., Vercauteren, D.P., Lucas, A.A. and André, J.-M., J. Catalysis, 119 (1989) 266.Google Scholar
  22. 22.
    Kuntz, I.D., Blaney, J.M., Oatley, S.J., Langridge, R. and Ferrin, T.E., J. Mol. Biol., 161 (1982) 269.Google Scholar

Copyright information

© ESCOM Science Publishers B.V 1994

Authors and Affiliations

  • Laurence Leherte
    • 1
  • Frank H. Allen
    • 1
  1. 1.Cambridge Crystallographic Data CentreCambridgeU.K.

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