Journal of Computer-Aided Molecular Design

, Volume 11, Issue 1, pp 79–92 | Cite as

MS-WHIM, new 3D theoretical descriptors derived from molecular surface properties: A comparative 3D QSAR study in a series of steroids

  • Gianpaolo Bravi
  • Emanuela Gancia
  • Paolo Mascagni
  • Monica Pegna
  • Roberto Todeschini
  • Andrea Zaliani

Abstract

The recently proposed WHIM (Weighted Holistic Invariant Molecular) approach [Todeschini,R., Lasagni, M. and Marengo, E., J. Chemometrics, 8 (1994) 263] has been applied tomolecular surfaces to derive new 3D theoretical descriptors, called MS-WHIM. To test theirreliability, a 3D QSAR study has been performed on a series of steroids, comparing the MS-WHIM description to both the original WHIM indices and CoMFA fields. The analysis of thestatistical models obtained shows that MS-WHIM descriptors provide meaningful quantitativestructure–activity correlations. Thus, the results obtained agree well with thoseachieved using CoMFA fields. The concise number of indices, the ease of their calculationand their invariance to the coordinate system make MS-WHIM an attractive tool for 3DQSAR studies.

CoMFA Holistic description Connolly surface PCA Experimental design PLS 

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References

  1. 1.
    Cramer III, R.D., DePriest, S.A., Patterson, D.E. and Hecht, P., In Kubinyi, H. (Ed.) 3D QSAR in Drug Design: Theory, Methods and Applications, ESCOM, Leiden, The Netherlands, 1993, pp. 443–485.Google Scholar
  2. 2.
    Bradshaw, J., Wynn, E.W., Salt, D.W. and Ford, M.G., In Wermuth, C.G. (Ed.) Trends in QSAR and Molecular Modelling 92 (Proceedings of the 9th European Symposium on Structure–Activity Relationships: QSAR and Molecular Modelling), ESCOM, Leiden, The Netherlands, 1993, pp. 220–224.Google Scholar
  3. 3.
    Broto, P., Moreau, G. and Vandycke, C., Eur. J. Med. Chem.–Chim. Ther., 19 (1984) 66.Google Scholar
  4. 4.
    Clementi, S., Cruciani, G., Riganelli, D., Valigi, R., Costantino, G., Baroni, M. and Wold, S., Pharm. Pharmacol. Lett., 3 (1993) 5.Google Scholar
  5. 5.
    Todeschini, R., Lasagni, M. and Marengo, E., J. Chemometr., 8 (1994) 263.Google Scholar
  6. 6.
    Todeschini, R., Gramatica, P., Provenzani, R. and Marengo, E., Chemometr. Intell. Lab. Syst., 27 (1995) 221.Google Scholar
  7. 7.
    Todeschini, R., Vighi, M., Provenzani, R., Finizio, A. and Gramatica, P., Chemosphere, 8 (1996) 1527.Google Scholar
  8. 8.
    Todeschini, R., Moro, G., Boggia, R., Bonati, L., Cosentino, U., Lasagni, M. and Pitea, D., Chemometr. Intell. Lab. Syst., in press.Google Scholar
  9. 9.
    Cramer III, R.D., Patterson, D.E. and Bunce, J.D., J. Am. Chem. Soc., 110 (1988) 5959.Google Scholar
  10. 10.
    Oprea, T.I., Ciubotariu, D., Sulea, T.I. and Simon, Z., Quant. Struct.–Act. Relatsh., 12 (1993) 21.Google Scholar
  11. 11.
    Good, A.C., So, S. and Richards, W.G., J. Med. Chem., 36 (1993) 433.Google Scholar
  12. 12.
    Good, A.C., Peterson, S.J. and Richards, W.G., J. Med. Chem., 36 (1993) 2929.Google Scholar
  13. 13.
    Jain, N.A., Koile, K. and Chapman, D., J. Med. Chem., 37 (1994) 2315.Google Scholar
  14. 14.
    Dunn, J.F., Nisula, B.C. and Rodbard, D., J. Clin. Endocrin. Metab., 53 (1981) 58.Google Scholar
  15. 15.
    Joliffe, I.T., Principal Components Analysis, Springer, New York, NY, U.S.A., 1986.Google Scholar
  16. 16.
    Box, G.E.P., Hunter, W.G. and Hunter, J.S., Statistics for Experimenters, Wiley, New York, NY, U.S.A., 1978.Google Scholar
  17. 17.
    Clementi, S., Cruciani, G., Baroni, M. and Costantino, G., In Kubinyi, H. (Ed.) 3D QSAR in Drug Design: Theory, Methods and Applications, ESCOM, Leiden, The Netherlands, 1993, pp. 570–572.Google Scholar
  18. 18.
    Wold, S., Albano, C., Dunn III, W.J., Edlund, U., Ebsen, K., Geladi, P., Hellberg, S., Johansson, E., Lindberg, W. and Sjostrom, M., In Kowalsky, B.R. (Ed.) Chemometrics, Reidel, Dordrecht, The Netherlands, 1984, p. 17.Google Scholar
  19. 19.
    Westphal, U., Steroid–Protein Interactions II, Springer, Berlin, Germany, 1986.Google Scholar
  20. 20.
    Roberts, S.M., Symposia in Print: Molecular Recognition in Chemistry and Biochemistry Problems, Royal Society, London, U.K., 1989.Google Scholar
  21. 21.
    Connolly, M., QCPE Bull., 1 (1981) 75.Google Scholar
  22. 22.
    Weiner, P., Langridge, R., Blaney, J.M., Schefer, R. and Kollman, P.A., Proc. Natl. Acad. Sci. USA, 79 (1982) 3754.Google Scholar
  23. 23.
    SYBYL molecular modeling system, available from Tripos Associates, Inc., St. Louis, MO, U.S.A.Google Scholar
  24. 24.
    Baroni, M., Costantino, G., Cruciani, G., Riganelli, D., Valigi, R. and Clementi, S., Quant. Struct.–Act. Relatsh., 12 (1993) 9.Google Scholar
  25. 25.
    Kearsley, S.K. and Smith, G.M., Tetrahedron Comput. Methodol., 3 (1990) 616.Google Scholar
  26. 26.
    Clark, M., Cramer III, R.D. and Van Opdenbosch, N., J. Comput. Chem., 7 (1986) 230.Google Scholar
  27. 27.
    Gasteiger, J. and Marsili, M., Tetrahedron, 36 (1980) 3219.Google Scholar
  28. 28.
    Klebe, G., Mietzner, T. and Weber, F., J. Comput.-Aided Mol. Design, 8 (1994) 751.Google Scholar
  29. 29.
    Wold, S., Technometrics, 20 (1978) 397.Google Scholar
  30. 30.
    Kubinyi, H. and Abraham, U., In Kubinyi, H. (Ed.) 3D QSAR in Drug Design: Theory, Methods and Applications, ESCOM, Leiden, The Netherlands, 1993, pp. 717–728.Google Scholar
  31. 31.
    Manallack, D.T., Ellis, D.D. and Livingstone, D.J., J. Med. Chem., 37 (1994) 3758.Google Scholar
  32. 32.
    Manallack, D.T. and Livingstone, D.J., Med. Chem. Res., 2 (1992) 181.Google Scholar
  33. 33.
    Folkers, G., Merz, A. and Rognan, D., In Kubinyi, H. (Ed.) 3D QSAR in Drug Design: Theory, Methods and Applications, ESCOM, Leiden, The Netherlands, 1993, pp. 583–618.Google Scholar
  34. 34.
    Audry, E., Dubost, J.P., Colleter, J.C. and Dallet, P., Eur. J. Med. Chem.–Chim. Ther., 21 (1986) 71.Google Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Gianpaolo Bravi
    • 1
  • Emanuela Gancia
    • 1
  • Paolo Mascagni
    • 1
  • Monica Pegna
    • 1
  • Roberto Todeschini
    • 2
  • Andrea Zaliani
    • 1
  1. 1.Italfarmaco Research CentreCinisello Balsamo (Milan)Italy
  2. 2.Department of Environmental SciencesUniversity of MilanMilanItaly

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