Skip to main content

Molecular modelling in drug design

  • Conference paper
Chemical Information

Abstract

The concept that organic molecules may be regarded as collections of generally spherical atoms, connected to one another by rod-like bonds is well-established and has, for many years, provided the basis upon which chemists visualise structures, in either two or three dimensions. Fabrication of atoms and bonds from wood, metal or plastic has been done increasingly since 1950; an important property of such physical models is that they can be made to be dimensionally accurate. Thus the well-known Dreiding models [1], designed by André Dreiding are constructed from stainless steel and preserve bond lengths and bond angles, while reducing all atoms to points with zero atomic radius. The CPK models [2] on the other hand, generally built with a plastic material, have atoms of the correct radius and also preserve bond lengths and bond angles. Both of these, and other types of models are used commonly by chemists who are concerned with the overall shape of molecules, a property that is clearly important in determining their behaviour.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Drieding models, designed by Drieding at the University of Zurich, as available from Fisher Scientific (Pittsburgh, PA).

    Google Scholar 

  2. The Corey-Pauling-Koltun (CPK) models were designed by Corey and Pauling in the 1940s and use connectors that were designed by Koltun. CPK models are available from Harvard Apparatus Inc., ( S.Matick, MA).

    Google Scholar 

  3. SYBYL is produced by Tripos Associates Inc., 1699 S. Hanley Road, Suite 303, St. Louis, MO, 63144.

    Google Scholar 

  4. QUANTA is produced by Polygen Inc., 200 Fifth Avenue, Waltham, MA, 02254.

    Google Scholar 

  5. Yarchoan, R., Mitsuya, H., and Broder, S/.Scientific American, 259, 110–119. (1988).

    Article  Google Scholar 

  6. Cheng, Y.-C., Dutschman, G.E., Bastow, K.F., Sarngadharan, M.G., and Ting, R. Y. C. r J. Biol Chem.: 262, 2187–2189, ( 1987.

    Google Scholar 

  7. See, for example, Goldstein, A., Aronow, L., and Kalman, S.M. Principles of Drug Action’ 2nd. Edition. Wiley & Sons, New York (1974), pp. 184–197. See also: Greig, N.H.: Cancer Treatment Rev.: 14, 1–10, (1987).

    Google Scholar 

  8. Balzarini, J., Mitsuya, H., DeClercq, E., and Broder S.: Int. J. Cancer, 37,451 S.M. Principles of Drug Action’ 2nd. Edition. Wiley & Sons, New York (1974), pp. 184–197. See also: Greig, N.H.: Cancer Treatment Rev.:14, 1–10,(1987).457, (1986): Mitsuya, H., Weinhold, K.J., Furman, P.A., Clair, M.H., Lehrman, S.M., Gallo, R.C., Bolgnesi, D., Barry, D.W., and Border, S.J roc. Natl. Acad. U.S.A.: 82,7096 S.M. Principles of Drug Action’ 2nd. Edition. Wiley & Sons, New York (1974), pp. 184–197. See also: Greig, N.H.: Cancer Treatment Rev.:14, 1–10, (1987). 7100, (1985).

    Google Scholar 

  9. Mitsuya, H., and Broder, S.: Proc. Natl Acad. Sci. U.S.A.: 83, 1911 S.M. Principles of Drug Action’ 2nd. Edition. Wiley & Sons, New York (1974), pp. 184–197. See also: Greig, N.H.: Cancer Treatment Rev.:14, 1–10, (1987). 1915, (1986).

    Google Scholar 

  10. York, J. L. J. Org. Chem.: 46, 2171–2173, (1981).

    Article  Google Scholar 

  11. Fauci, A.S.: Science: 239, 617–619, (1988): Price, R.W., Brew, B., Sidtis, J., Rosenblum, M., Scheck, A.C., and Cleary, P.-.Science: 239, 586-589, (1988): Berger, J.R., and Resnick, L. in ‘AIDS. Modern Concepts and Therapeutic Challenges’. Broder, S., (Ed.). M. Dekker, New York (1987), pp. 263–283: Lane, H.C., and Fauci, A.S.: in ‘AIDS. Modern Concepts and Therapeutic Challenges’. Broder, S., (Ed.). M. Dekker, New York (1987), pp. 185–203.

    Article  Google Scholar 

  12. Craig, P.N.: J. Med. Chem.: 14, 680–684, (1971).

    Article  Google Scholar 

  13. Iwasa, J., Fujita, T., and Hansch, C.: J. Med. Chem.: 8,150–158, (1965): Hansch, C., Leo, A., Unger, S., Kim, K.H., Nikaitani, S., and Lien, E.J.: J. Med. Chem.: 16,1207–1216, (1973): Leo, A., and Hansch, C.: Chem. Rev.: 71, 525–548, (1971).

    Google Scholar 

  14. Marquez, V.E., Tseng, C.K.-H., Kelley, J.A., Mitsuya, H., Broder, S., Roth, J.S., and Driscoll, J.S.: Biochem. Pharmacol: 36, 2719–2733, (1987).

    Article  Google Scholar 

  15. Driscoll, J.S., Marquez, V.E., Barchi, J., and Ford, H., Cooney, D.A., Mitsuya, H., Aoki, S., Kelley, J., Johns, D., Broder, S., and Flora, K.:Intnl. AIDS Conf., Montreal (1989), paper MCP–107.

    Google Scholar 

  16. Mitsuya, H., Dahlberg, J.E., Spigelman, Z., Matsushita, S., Jarrett, R.F., Matsukura, M., Currens, M.J., Aaronson, S.A., Reitz, M., McCaffrey, R.S., and Broder, S.:Human Retroviruses, Cancer, and AIDS: Approaches to Prevention and Therapy. Alan R. Liss (1988). pp 407–421.

    Google Scholar 

  17. Webb. T.R., Mitsuya, H., and Broder, S.: J. Med. Chem.: 31, 1475–1479, (1988).

    Article  Google Scholar 

  18. Nishizuka, Y.: Nature, 308, 693-698, (1984): Jetten, A.M., Ganong, B.R., Vandenbark, G.R., Shirley, J.E., and Bell, R.M.: Proc. Natl Acad. Sci. U.S.A.: 82,1941–1945, (1985): Jeng, A.Y., Lichti, U., Strickland, J.E., and Blumberg, P.M.: Cancer Res.: 45,5714–5721, (1985): Sharkey, N.A., Leach, K.L., and Blumberg, P.M.: Proc, Natl, Acad. Sci. U.S.: 81, 607–610, (1984).

    Google Scholar 

  19. Laughton, C.A., Dale, I.L., and Gescher, A.: J. Med. Chem.: 32, 428–433, (1989).

    Article  Google Scholar 

  20. McPhail, A.T., McPhail, D.R., Wani, M.C., Wall, M.E., and Nicholas, A.W.: J. Matl Prod.: 52, 212–216, (1989).

    Article  Google Scholar 

  21. Nishino, H., Nishino, A., Takayasu, J., Hasegawa, T., Iwashima, A., and Hirabayashi, K: Cancer Res.: 48, 5210–5215, (1988).

    Google Scholar 

  22. Jakes, S.E., andWillett,P.:J. Mol. Graph.: A, 12-20,(1986): Jakes, S.E., Watts, N., Willett, P., Bawden, D., and Fisher, J.D.: J. Mil Graph..: 5, 41–49, (1987). We are very grateful to Dr. Trevor Devon (Pfizer UK, Sandwich, Kent, UK) for his assistance in carrying out three-dimensional coordinate searches of the Cambridge Crystal Database.

    Google Scholar 

  23. Sheridan, R.P., Rusinko, A., Nilakantan, R., and Venkataraghavan, R.:Proc. Natl. Acad. Sci. U.S.A. : In press (1989). We are very grateful to Dr. Babu Venkataraghavan (Lederle Laboratories, Pearl River, NY) for his assistance in carrying out three-dimensional coordinate searches of the Cambridge Crystal Database.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Milne, G.W.A., Driscoll, J.S., Marquez, V.E. (1989). Molecular modelling in drug design. In: Collier, H.R. (eds) Chemical Information. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75165-3_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-75165-3_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-51804-4

  • Online ISBN: 978-3-642-75165-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics