Skip to main content
SpringerLink
Log in

The atom assignment problem in automated de novo drug design. 4. Tests for site-directed fragment placement based on molecular complementarity

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

Summary

Three previous papers in this series have outlined an optimization method for atom assignment in drug design using fragment placement. In this paper the procedure is rigorously tested on a selection of five ligand-protein co-crystals. The algorithm is presented with the molecular graph of the ligand, and the electrostatic/hydrophobic potential of the site, with the aim of creating a placement on the molecular graph which is as electrostatically complementary or hydrophobically similar to the site as possible. Various designer options were tested, including, where appropriate, hydrogen bonding and a restricted number of halogens. In most cases, the placement obtained was at least as good as the native ligand, if not significantly better.

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. Barakat, M.T. and Dean, P.M., J. Comput.-Aided Mol. Design, 9 (1995) 341.

    Google Scholar 

  2. Barakat, M.T. and Dean, P.M., J. Comput.-Aided Mol. Design, 9 (1995) 351.

    Google Scholar 

  3. Barakat, M.T. and Dean, P.M., J. Comput.-Aided Mol. Design, 9 (1995) 359.

    Google Scholar 

  4. Barakat, M.T. and Dean, P.M., J. Comput.-Aided Mol. Design, 9 (1995) 457.

    Google Scholar 

  5. Diederichs, K. and Schultz, G.E., J. Mol. Biol., 217 (1991) 541.

    Google Scholar 

  6. Weber, I.T. and Steitz, T.A., J. Mol. Biol., 198 (1987) 311.

    Google Scholar 

  7. Davies, J.F., Delcamp, T.L., Prendergast, N.J., Ashford, V.A., Freisheim, J.H. and Kraut, J., Biochemistry, 29 (1990) 9467.

    Google Scholar 

  8. Schreuder, H.A., Van der, Laan, J.M., Hol, W.G.J. and Drenth, J., J. Mol. Biol., 199 (1988) 637.

    Google Scholar 

  9. Cowan, S.W., Newcomer, M.E. and Jones, T.A., Protein Struct. Funct. Genet., 8 (1990) 44.

    Google Scholar 

  10. Ptitsyn, O.B., Zanotti, G., Denesyuk, A.L. and Bychkova, V.E., FEBS Lett., 317 (1993) 181.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Drug Design Group, Department of Pharmacology, University of Cambridge, Tennis Court Road, CB2 1QJ, Cambridge, U.K.

    M. T. Barakat & P. M. Dean

Authors
  1. M. T. Barakat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. M. Dean
    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

Barakat, M.T., Dean, P.M. The atom assignment problem in automated de novo drug design. 4. Tests for site-directed fragment placement based on molecular complementarity. J Computer-Aided Mol Des 9, 448–456 (1995). https://doi.org/10.1007/BF00124002

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00124002

Keywords

Search

Navigation