SPROUT, HIPPO and CAESA: Tools for de novo structure generation and estimation of synthetic accessibility

Summary

Several components of a system for structure generation are now well developed. HIPPO is a program that characterises a receptor binding site for potential target sites within the cavity that can be used in de novo design. The target sites include simple and complex hydrogen bonds, covalent bonds and bonds to metal ions. The SPROUT program for structure generation consists of two main components: the first is skeleton generation, followed by atom substitution to convert the solution skeletons to molecules. A new method of skeleton generation is presented here, where part skeletons are grown outwards from each target site. The part skeletons are then connected together to form solution skeletons. Finally the CAESA program is described, that ranks the output from SPROUT according to ease of synthesis.

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References

  1. 1

    Gillet, V.J., Newell, W., Mata, P., Myatt, G., Sike, S., Zsoldos, Z. and Johnson, A.P., J. Chem. Inf. Comput. Sci., 34 (1994) 207.

    Google Scholar 

  2. 2

    Gillet, V.J., Johnson, A.P., Mata, P., Sike, S. and Williams, P., J. Comput.-Aided Mol. Design, 7 (1993) 127.

    Google Scholar 

  3. 3

    Gillet, V.J., Johnson, A.P., Mata, P. and Sike, S., Tetrahedron Comput. Methodol., 3 (1990) 681.

    Google Scholar 

  4. 4

    Mata, P., Gillet, V.J., Johnson, A.P., Lampreia, J., Myatt, G.J., Sike, S. and Stebbings, A.L., J. Chem. Inf. Comput. Sci., 35 (1995) 479.

    Google Scholar 

  5. 5

    Goodford, P.J., J. Med. Chem., 28 (1985) 849.

    Google Scholar 

  6. 6

    Tomioka, N. and Itai, A., J. Comput.-Aided Mol. Design, 8 (1994) 347.

    Google Scholar 

  7. 7

    Danziger, D.J. and Dean, P.M., Proc. R. Soc. London Ser. B., 236 (1989) 115.

    Google Scholar 

  8. 8

    Böhm, H.-J., J. Comput.-Aided Mol. Design, 6 (1992) 61.

    Google Scholar 

  9. 9

    Böhm, H.-J., J. Comput.-Aided Mol. Design, 6 (1992) 593.

    Google Scholar 

  10. 10

    Jeffrey, G.A. and Saenger, W., Hydrogen Bonding in Biological Structures, Springer, Heidelberg, 1991.

    Google Scholar 

  11. 11

    Dickerson, R.E. and Geis, I., The Structure and Action of Proteins, W.A. Benjamin, Reading, MA, 1969.

    Google Scholar 

  12. 12

    Abola, E.E., Bernstein, F.C. and Koetzle, T.F., The Role of Data in Scientific Progress, Elsevier, Amsterdam, 1985.

    Google Scholar 

  13. 13a.

    Zhou, W.G., Guo, J., Huang, W., Fletterick, R.J. and Scanlan, T.S., Science, 265 (1994) 1059.

    Google Scholar 

  14. 13b.

    Blackburn, S., Enzyme Structure and Function, Marcel Dekker, New York, NY, 1976.

    Google Scholar 

  15. 14

    Lewis, R.A. and Leach, A.R., J. Comput.-Aided Mol. Design, 8 (1994) 467.

    Google Scholar 

  16. 15

    Eisen, M., Wiley, D., Karplus, M. and Hubbard, R.E., Protein Struct. Funct. Genet., 19 (1994) 199.

    Google Scholar 

  17. 16

    Miranker, A. and Karplus, M., Protein Struct. Funct. Genet., 11 (1991) 29.

    Google Scholar 

  18. 17

    Allen, F.H., Bellard, S., Brice, M.D., Cartwright, B.A., Doubleday, A., Higgs, H., Hummelink, T., Hummelink-Peters, B.G., Kennard, O., Motherwell, W.D.S., Rodgers, J.R. and Watson, D.G., Acta Crystallogr., B35 (1979) 2331.

    Google Scholar 

  19. 18

    Nishibata, Y. and Itai, A., J. Med. Chem., 36 (1993) 2921.

    Google Scholar 

  20. 19

    Rotstein, S.H. and Murcko, M.A., J. Comput.-Aided Mol. Design, 7 (1993) 23.

    Google Scholar 

  21. 20

    Rotstein, S.H. and Murcko, M.A., J. Med. Chem., 36 (1993) 1700.

    Google Scholar 

  22. 21

    Moon, J.B. and Howe, W.J., Protein Struct. Funct. Genet., 11 (1991) 314.

    Google Scholar 

  23. 22

    Weininger, D., Dixon, S.J. and Blaney, J.M., Lecture presented at The Molecular Graphics Society Meeting on Bonding Sites, York, March 1993.

  24. 23

    Payne, A. and Glen, R.C., Lecture presented at The Molecular Graphics Society Meeting on Bonding Sites, York, March 1993.

  25. 24

    Miranker, A., Lecture presented at The Molecular Graphics Society Meeting on Bonding Sites, York, March 1993.

  26. 25

    Lewis, R.A., Roe, D.C., Huang, C., Ferrin, T.E., Langridge, R. and Kuntz, I.D., J. Mol. Graphics, 10 (1992) 66.

    Google Scholar 

  27. 26

    Nilsson, N.J., Principles of Artificial Intelligence, Springer, Heidelberg, 1982.

    Google Scholar 

  28. 27

    Available Chemicals Directory, MDL Information Systems, Inc., San Leandro, CA.

  29. 28

    Pearl, J., Probabilistic Reasoning in Intelligent Systems: Networks of Plausible Inference, Morgan Kaufmann, San Mateo, CA, 1988.

    Google Scholar 

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Correspondence to A. Peter Johnson.

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Gillet, V.J., Myatt, G., Zsoldos, Z. et al. SPROUT, HIPPO and CAESA: Tools for de novo structure generation and estimation of synthetic accessibility. Perspectives in Drug Discovery and Design 3, 34–50 (1995). https://doi.org/10.1007/BF02174466

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Keywords

  • Hydrogen
  • Polymer
  • Hydrogen Bond
  • Binding Site
  • Structure Generation