Journal of Computer-Aided Molecular Design

, Volume 6, Issue 5, pp 461–474 | Cite as

Ligand atom partial charges assignment for complementary electrostatic potentials

  • S. L. Chan
  • P. L. Chau
  • J. M. Goodman
Research Papers


The design of molecules to fit into the active site of receptors is a rapidly developing area of pharmacology and medicinal chemistry. A good ligand needs a suitable geometry and also appropriate electrostatic properties. The electrostatic properties of the ligand should complement those of the receptor. We present a method for the assignment of atom-centred point charges for a ligand, based on the electrostatic potential of the receptor. These point charges are chosen to give the best possible complementarity to the receptor electrostatic potential over the van der Waals surface of the ligand. We demonstrate that point charges can be chosen to give good electrostatic complementarity, and suggest that a molecule with similar electrostatic properties should bind well to the receptor.

Key words

Drug design Molecular electrostatic potential 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kuntz, I.D., Blaney, J.M., Oatley, S.J., Langridge, R. and Ferrin, T.E., J. Mol. Biol., 161 (1982) 269.Google Scholar
  2. 2.
    DesJarlais, R.L., Sheridan, R.P., Dixon, J.S., Kuntz, I.D. and Venkataraghavan, R., J. Med. Chem., 29 (1986) 2149.Google Scholar
  3. 3.
    DesJarlais, R.L., Sheridan, R.P., Seibel, G.L., Dixon, J.S., Kuntz, I.D. and Venkataraghavan, R., J. Med. Chem., 31 (1988) 722.Google Scholar
  4. 4.
    Lewis, R.A. and Dean, P.M., Proc. R. Soc. Lond., B236 (1989) 125Google Scholar
  5. 5.
    Lewis, R.A. and Dean, P.M., Proc. R. Soc. Lond., B236 (1989) 141.Google Scholar
  6. 6.
    Lewis, R.A., J. Comput.-Aided Mol. Design, 4 (1990) 205.Google Scholar
  7. 7.
    Browman, M.J., Carruthers, L.M., Kashuba, K.L., Momany, F.A., Pottle, M.S., Rosen, S.P. and Rumsey, S.M., QCPE, 11 (1975) programme 286.Google Scholar
  8. 8.
    Némethy, G., Pottie, M.S. and Scheraga, H.A., J. Phys. Chem., 87 (1983) 1883.Google Scholar
  9. 9.
    Pople, J.A., Santry, D.P. and Segal, G.A., J. Chem. Phys., 43 (1965) S129.Google Scholar
  10. 10.
    Segal, G.A. and Pople, J.A., J. Chem. Phys., 43 (1965) S136.Google Scholar
  11. 11.
    Nakamura, H., Komatsu, K., Nakagawa, S. and Umeyama, H., J. Mol. Graphics, 3 (1985) 2.Google Scholar
  12. 12.
    Náray-Szabó, G., J. Mol. Graphics, 7 (1989), 76.Google Scholar
  13. 13.
    Dean, P.M., Chau, P.-L. and Barakat, M.T., J. Mol. Struct., 256 (1992) 75.Google Scholar
  14. 14.
    Chirlian, L.E. and Francl, M.M., J. Comput. Chem., 8 (1987) 894.Google Scholar
  15. 15.
    Momany, F.A., J. Phys. Chem., 82 (1978) 592.Google Scholar
  16. 16.
    Cox, S.R. and Williams, D.E., J. Comput. Chem., 2 (1981) 304.Google Scholar
  17. 17.
    Singh, U.C. and Kollman, P.A., J. Comput. Chem., 5 (1984) 129.Google Scholar
  18. 18.
    Chau, P.-L. and Dean, P.M., J. Mol. Graphics, 5 (1987) 97.Google Scholar
  19. 19.
    Lee, B. and Richards, F.M., J. Mol. Biol., 55 (1971) 379.Google Scholar
  20. 20.
    Chau, P.L. and Dean, P.M., J. Comput.-Aided Mol. Design, 6 (1992) 407.Google Scholar
  21. 21.
    Watson, H.C., Walker, N.P.C., Shaw, P.J., Bryant, T.N., Wendell, P.L., Fothergill, L.A., Perkins, R.E., Conroy, S.C., Dobson, M.J., Tuite, M.F., Kingsman, A.J. and Kingsman, S.M., EMBO J., 1 (1982) 1635.Google Scholar

Copyright information

© ESCOM Science Publishers B.V. 1992

Authors and Affiliations

  • S. L. Chan
    • 1
  • P. L. Chau
    • 2
  • J. M. Goodman
    • 3
  1. 1.Department of Molecular and Medical GeneticsUniversity of TorontoCanada
  2. 2.School of Clinical MedicineUniversity of CambridgeCambridgeU.K.
  3. 3.Department of ChemistryUniversity of CambridgeCambridgeU.K.

Personalised recommendations