Skip to main content
SpringerLink
Log in
Book cover

International Conference on Evolutionary Programming

EP 1998: Evolutionary Programming VII pp 449–461Cite as

Fully automated and rapid flexible docking of inhibitors covalently bound to serine proteases

  • Conference paper
  • First Online:

Part of the book series: Lecture Notes in Computer Science ((LNCS,volume 1447))

Abstract

Viral serine proteases have become increasingly attractive targets for rational drug design. Many known inhibitors of serine proteases form a covalent bond to the activated serine oxygen, an interaction not taken into account by available docking software used for database mining. We describe a new method for the fully automated and rapid flexible docking of inhibitors covalently bound to serine proteases. The method combines an energy function specifically tuned for molecular docking and an evolutionary programming search engine, and takes advantage of the constained geometry about the site of covalent attachment to dramatically limit the search space and increase search efficiency. Results for several test systems are presented, including a database search which yielded a known inhibitor as a highranking compound.

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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literature cited

  1. Kuntz, I. D.; Meng, E. C.; Shoichet, B. K. Accts. Chem. Res. 1994, 27, 117–123.

    Google Scholar 

  2. Jones, G.; Willett, P., Glen, R. C.; Leach, A. R.; Taylor, R. J. Mol. Biol. 1997, 267, 727–748.

    Google Scholar 

  3. Kuntz, I. D.; Makino, S. J. Comp. Chem, 1997, 18, 1812–1825.

    Google Scholar 

  4. Desmet, J.; Wilson, I. A.; Joniau, M.; DeMaeyer, M.; Lasters, I. FASEB J. 1997, 11, 164–172.

    Google Scholar 

  5. Welch, W.; Ruppert, J.; Jain, A. N. Chem. Biol. 1996, 3, 449–463.

    Google Scholar 

  6. Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. J. Mol. Biol. 1996, 261, 470–489.

    Google Scholar 

  7. Gehlhaar, D. K.; Verkhivker, G. M.; Rejto, P. A.; Sherman, C. J.; Fogel, D. B.; Fogel, L. J.; Freer, S. T. Chem. Biol. 1995, 2, 317–324.

    Google Scholar 

  8. Chen, P.; Tsuge, H.; Almassy, R. J.; Gribskov, C. L.; Katoh, S.; Vanderpool, D. L.; Margosiak, S. A.; Pinko, C; Matthews, D. A.; Kan, C.-C. Cell 1996, 86, 835–843.

    Google Scholar 

  9. Love, R. A.; Parge, H. E.; Wickersham, J. A.; Hostomsky, Z.; Habuka, N.; Moomaw, E. W.; Adachi, T.; Hostomska, Z. Cell 1996, 86, 331–342.

    Google Scholar 

  10. Kim, J. L. Morgenstern, K. A.; Lin, C.; Fox, T.; Dwyer, M. D.; Landro, J. A.; Chambers, S. P.; Markland, W.; Lepre, C. A.; O'Malley, E. T.; Harbeson, S. L.; Rice, C. M.; Murcko, M. A.; Caron, P. R.; Thomson, J. A. Cell 1996, 87, 343–355.

    Google Scholar 

  11. Babine, R. E.; Bender, S. L. Chem. Rev. 1997, 97, 1359–1472.

    Google Scholar 

  12. Wlodawer, A.; Erickson, J. W. Annu. Rev. Biochem. 1993, 62, 543–585.

    Google Scholar 

  13. Appelt, K.; Bacquet, R. J.; Bartlett, C. A.; Booth, C. L.; Freer, S. T.; Fuhry, M. A. M.; Gehring, M. R.; Herrmann, S. M.; Howland, E. F.; Janson, C. A.; Jones, T. R.; Kan, C.; Kathardekar, V.; Lewis, K. K.; Marzoni, G. P.; Matthews, D. A.; Mohr, C.; Moomaw, E. W.; Morse, C. A.; Oatley, S. J.; Ogden, R. C.; Reddy, M. R.; Reich, S. H.; Schoettlin, W. S.; Smith, W. W.; Varney, M. D.; Villafranca, J. E.; Ward, R. W.; Webber, S.; Webber, S. E.; Welsh, K. M.; White, J. J. Med. Chem. 1991, 34, 1925–1934.

    Google Scholar 

  14. LaFemina, R. L.; Bakshi, K.; Long, W. J.; Pramanik, B.; Veloski, C. A.; Wolanski, B. S.; Marcy, A.; Hazuda, D. J. J. Virology 1996, 70, 4819–4824.

    Google Scholar 

  15. Mayo, S. L.; Olafson, B. D.; Goddard, W. A. J. Phys. Chem. 1990, 94, 8897–8909.

    Google Scholar 

  16. Fogel, D.B. Evolutionary Computation: Towards a New Philosophy of Machine Intelligence. IEEE Press: New York, NY, 1995; 75–155.

    Google Scholar 

  17. Hall, S. R.; Allen, F. H.; Brown, I. D. Acta Cryst. 1991, A47, 655–685.

    Google Scholar 

  18. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Kiskamp, M.; Caufield, C; Chang, G.; Hendrickson, T.; Still, W. C. J. Comput. Chem. 1990, 11, 440–467.

    Google Scholar 

  19. Weiner, S. J.; Kollman, P. A.; Case, D. A.; Singh, U. C.; Ghio, C.; Algona, G.; Profeta, S. Jr.; Weiner, P. J. J. Am. Chem. Soc. 1984, 106, 765–784.

    Google Scholar 

  20. Bernstein, F. C.; Koetzle, T. F.; Williams, G. J.; Meyer, E. F. Jr.; Brice, M. D.; Rodgers, J. R.; Kennard, O.; Shimanouchi, T.; Tasumi, M. J. Mol. Biol. 1977, 112, 535–542.

    Google Scholar 

  21. Rose, P. W. In Computer-Assisted Molecular Design Course, UCSF; San Francisco, CA, 1997; Chapter 12.

    Google Scholar 

  22. Bohm, H. J. J. Comput. Aided Mol. Des. 1994, 8, 243–256.

    Google Scholar 

  23. McDonald, I. K.; Thornton, J. M. J. Mol. Biol. 1994, 238, 777–793.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Agouron Pharmaceuticals, Inc., 3301 North Torrey Pines Court, 92037, La Jolla, CA

    Daniel K. Gehlhaar, Djamal Bouzida & Paul A. Rejto

Authors
  1. Daniel K. Gehlhaar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Djamal Bouzida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul A. Rejto
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

V. W. Porto N. Saravanan D. Waagen A. E. Eiben

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Gehlhaar, D.K., Bouzida, D., Rejto, P.A. (1998). Fully automated and rapid flexible docking of inhibitors covalently bound to serine proteases. In: Porto, V.W., Saravanan, N., Waagen, D., Eiben, A.E. (eds) Evolutionary Programming VII. EP 1998. Lecture Notes in Computer Science, vol 1447. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0040797

Download citation

  • DOI: https://doi.org/10.1007/BFb0040797

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-64891-8

  • Online ISBN: 978-3-540-68515-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation