Advertisement

Journal of Computer-Aided Molecular Design

, Volume 16, Issue 8–9, pp 653–681 | Cite as

A comparison of the pharmacophore identification programs: Catalyst, DISCO and GASP

  • Yogendra Patel
  • Valerie J. GilletEmail author
  • Gianpaolo Bravi
  • Andrew R. Leach
Article

Abstract

Three commercially available pharmacophore generation programs, Catalyst/HipHop, DISCO and GASP, were compared on their ability to generate known pharmacophores deduced from protein-ligand complexes extracted from the Protein Data Bank. Five different protein families were included Thrombin, Cyclin Dependent Kinase 2, Dihydrofolate Reductase, HIV Reverse Transcriptase and Thermolysin. Target pharmacophores were defined through visual analysis of the data sets. The pharmacophore models produced were evaluated qualitatively through visual inspection and according to their ability to generate the target pharmacophores. Our results show that GASP and Catalyst outperformed DISCO at reproducing the five target pharmacophores.

pharmacophore identification protein ligand interactions pharmacophoric features structural alignment conformational flexibility 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Gund P., In Güner, O.F (Ed.) Pharmacophore Perception, Development, and Use in Drug Design, International University Line, La Jolla, CA, 2000, pp. 3–11.Google Scholar
  2. 2.
    Güner, O.F (Ed.) Pharmacophore Perception, Development, and Use in Drug Design, International University Line, La Jolla, CA, 2000.Google Scholar
  3. 3.
    Martin, Y.C., In Güner, O.F (Ed.) Pharmacophore Perception, Development, and Use in Drug Design, International University Line, La Jolla, CA, 2000, pp. 49–68.Google Scholar
  4. 4.
    Martin, Y.C., Bures, M.G., Danaher, E.A., DeLazzer, J., Lico, I. And Pavlik, P.A., J. Comput.-Aided Mol. Design, 7 (1993) 83.Google Scholar
  5. 5.
    Barnum, D., Greene, J., Smellie, A. and Sprague, P., J. Chem. Inf. Comput. Sci., 36 (1996) 563.Google Scholar
  6. 6.
    Clement, O.O. and Mehl, A.T., In Güner, O.F (Ed.) Pharmacophore Perception, Development, and Use in Drug Design, International University Line, La Jolla, CA, 2000, pp. 69–84.Google Scholar
  7. 7.
    Greene, J., Kahn, S., Savoj, H., Sprague, P. and Teig, S., J. Chem. Inf. Comput. Sci., 34 (1994) 1297.Google Scholar
  8. 8.
    Smellie, A., Teig, S.L. and Towbin, P., J. Comp. Chem., 16 (1995) 171.Google Scholar
  9. 9.
    Jones, G., Willett, P. and Glen, R.C. In: Güner, O.F (Ed.) Pharmacophore Perception, Development, and Use in Drug Design, International University Line, La Jolla, CA, 2000, pp. 85–106.Google Scholar
  10. 10.
    Jones, G., Willett, P. and Glen, R.C., J. Comput.-Aided Mol. Design, 9 (1995) 532.Google Scholar
  11. 18.
    The GASP manual. Tripos Inc. 1699 South Hanley Road, St. Louis, MO 63144-2913, US.Google Scholar
  12. 19.
    Banner, D.W. and Hadváry, P., J. Bio. Chem., 266 (1991) 20085.Google Scholar
  13. 20.
    Mathews, I.I., Padmanabhan, K.P. and Tulinsky, A., Biochemistry, 33 (1994) 13547.Google Scholar
  14. 21.
    Chen, Z., Li, Y., Mulichak, A.M., Lewis, S.D. and Shafer, J.A., Arch. Biochem. Biophys., 322 (1995) 198.Google Scholar
  15. 22.
    Katz, B.A., Clark, J.M., Finer-Moore, J.S., Jenkins, T.E., Johnson, C.R., Ross, M.J., Luong, C., Moore, W.R., and Stroud, R.M., Nature, 39 (1998) 608.Google Scholar
  16. 23.
    Lyle, T.A., Chen, Z., Appleby, S.D., Freidinger, R.M., Gardell, S.J., Lewis, S.D., Li, Y., Lyle, E.A., Lynch Jr., J.J., Mulichak A.M., Ng, A.S., Naylor-Olsen, A.M. and Sanders, W.M., Bioorg. Med. Chem. Letters, 7 (1997) 67.Google Scholar
  17. 24.
    Krishnan, R., Zhang, E., Hakansson, K., Arni, R.K., Tulinsky, A., Lim-Wilby, M.S.L., Levy, O.E., Semple, J.E. and Brunck, T.K., Biochemistry, 37 (1998) 12094.Google Scholar
  18. 25.
    Wagner, J., Kallen, J., Ehrhardt, C., Evenou, J.-P. and Wagner, D., J. Med. Chem., 41 (1998) 3664.Google Scholar
  19. 26.
    Conti, E., Rivetti, C., Wonacott, A. and Brick, P., FEBS Letters, 425 (1998) 229.Google Scholar
  20. 27.
    Jhoti, H., Cleasby, A., Reid, S., Thomas, P.J., Weir, M. and Wonacott, A., Biochemistry, 38 (1999) 7969.Google Scholar
  21. 28.
    Jeffrey, P. D., Russo, A. A., Polyak, K., Gibbs, E., Hurwitz, J., Massague, J., and Pavletich, N.P., Nature, 376 (1995) 313.Google Scholar
  22. 29.
    Lawrie, A. M., Noble, M. E., Tunnah, P., Brown, N. R., Johnson, L. N. and Endicott, J. A., Nat. Struct. Biol., 4 (1997) 796.Google Scholar
  23. 30.
    Shewchuk, L., Hassell, A., Wisely, B., Rocque, W., Holmes, W., Veal, J. and Kuyper, L. F., J. Med. Chem., 43 (2000) 133.Google Scholar
  24. 31.
    Arris, C. E., Boyle, F. T., Calvert, A. H., Curtin, N. J., Endicott, J. A., Garman, E. F., Gibson, A. E., Golding, B. T., Grant, S., Griffin, R. J., Jewsbury, P., Johnson, L. N., Lawrie, A. M., Newell, D. R., Noble, M. E. M., Sausville, E. A., Schultz, R. and Yu, W., J. Med.Chem., 43 (2000) 2797.Google Scholar
  25. 32.
    Davis, S. T., Benson, B. G., Bramson, H. N., Chapman, D. E., Dickerson, S. H., Dold, K. M., Eberwein, D. J., Edelstein, M., Frye, S. V., Gampe Jr. R. T., Griffin, R. J., Harris, P. A., Hassell, A. M., Holmes, W. D., Hunter, R. N., Knick, V. B., Lackey, K., Lovejoy, B., Luzzio, M. J., Murray, D., Parker, P., Rocque, W. J. and Shewch, L., Science, 291 (2001) 134.Google Scholar
  26. 33.
    Oefner, C., D'Arcy, A. and Winkler, F.K., Eur. J. Biochem., 174 (1988) 377. 681Google Scholar
  27. 34.
    Davies, J.F., Delcamp, T.J., Predergast, N.J., Ashford, V.A., Freisheim, J.H. and Kraut, J. Biochemistry, 29 (1990) 9467.Google Scholar
  28. 35.
    Lewis, W.S., Cody, V., Galitsky, N., Luft, J.R., Pangborn, W., Chunduru, S.K., Spencer, H.T., Appleman, J.R. and Blakley, R.L., J. Bio. Chem.,270 (1995) 5057.Google Scholar
  29. 36.
    Cody, V., Galitsky, N., Luft., J.R., Pangborn, W., Rosowsky, A. and Blakley, R.L., Biochemistry, 36 (1997) 13897.Google Scholar
  30. 37.
    Gangjee, A., Vidwans, A.P., Vasudevan, A., Queener, S.F., Kisliuk, R.L., Cody, V., Li, R., Galitsky, N., Luft, J.R., and Pangborn, W., J. Med. Chem., 41 (1998) 3426.Google Scholar
  31. 38.
    Hsiou, Y., Das, K., Ding, J., Clark Jr., A.D., Kleim, J-P., Rösner, M.,, Winkler, I., Riess, G., Hughes S.H. and Arnold, E., J. Mol. Biol., 284 (1998) 313.Google Scholar
  32. 39.
    Ren, J., Diprose, J., Warren, J., Esnouf, R.M., Bird, L.E., Ikemizu, S., Slater, M., Milton, J., Balzarini, J., Stuart, D.I. and Stammers, D.K., J. Biol. Chem., 275 (2000) 5633.Google Scholar
  33. 40.
    Esnouf, R.M., Ren J., Hopkins, A.L., Ross, C.K. Jones, E.Y., Stammers, D.K. and Stuart, D.I., Proc. Natl. Acad. Sci., 94 (1997) 3984.Google Scholar
  34. 41.
    Hopkins, A.L., Ren, J., Esnouf, R.M., Willcox, B.E., Jones, E.Y., Ross, C., Miyasaka, T., Walker, R.T., Tanaka, H., Stammers, D.K. and Stuart, D.I., J. Med. Chem., 39 (1996) 1589.Google Scholar
  35. 42.
    Ren, J., Esnouf, R.M., Hopkins, A.L., Jones, E.Y., Kirby, I., Keeling, J., Ross, C.K., Larder, B.A., Stuart, D.I. and Stammers, D.K., Proc. Natl. Acad. Sci., 95 (1998) 9518.Google Scholar
  36. 43.
    Ren, J., Esnouf, R.M., Hopkins, A.L., Warren, J., Balzarini, J., Stuart, D.I. and Stammers, D.K., Biochemistry, 37 (1998) 14394.Google Scholar
  37. 44.
    Das, K., Ding, J., Hsiou, Y., Clark Jr., A.D., Moereels, H., Koymans, L., Andries, K., Pauwels, R., Janssen, P.A.J., Boyer, P.L., Clark, P. Smith Jr. R.H., Kroeger Smith, M.B., Michejda, C.J., Hughes, S.H. and Arnold, E., J. Mol. Biol., 264 (1996) 1085.Google Scholar
  38. 405.
    Ren, J., Nichols, C., Bird, L.E., Fujiwara, T., Sugimoto, H., Stuart, D.I. and Stammers, D.K., J. Biol. Chem., 275 (2000) 14316.Google Scholar
  39. 46.
    Ren, J., Milton, J., Weaver, K. L., Short, S. A., Stuart, D. I., and Stammers, D. K., Structure, 8 (2000) 1089.Google Scholar
  40. 47.
    Ren, J.S., Esnouf, R., Garman, E., Somers, D., Ross, C., Kirby, I., Keeling, J., Darby, G., Jones, Y., Stuart, D., and Stammers, D., Nat. Struct. Biol., 2 (1995) 293.Google Scholar
  41. 48.
    Hausrath, A.C. and Matthews, B.W., J. Biol. Chem., 269 (1994) 18839.Google Scholar
  42. 49.
    Gaucher, J.F., Selkti, M., Tiraboschi, G., Prangé, T., Roques, B. P., Tomas, A. and Fournié-Zaluski, M.C., Biochemistry, 38 (1999) 12569.Google Scholar
  43. 50.
    Marchand-Geneste, N., Watson, K.A., Alsberg, B.K. and King, R.D., J. Med. Chem., 45 (2002) 399.Google Scholar
  44. 51.
    Holmes, M.A., and Matthews, B.W., Biochemistry, 20 (1981) 6912.Google Scholar
  45. 52.
    Holmes, M.A., Tronrud, D.E., and Matthews, B.W., Biochemistry, 22 (1983) 236.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Yogendra Patel
    • 1
  • Valerie J. Gillet
    • 1
    Email author
  • Gianpaolo Bravi
    • 2
  • Andrew R. Leach
    • 2
  1. 1.Krebs Institute for Biomolecular Research and Department of Information StudiesUniversity of SheffieldWestern Bank, SheffieldUnited Kingdom
  2. 2.Evotec OAIAbingdon, OxonUK

Personalised recommendations