Summary
In this article, we review the use of in vitro and in silico affinity fingerprints as novel descriptors for similarity searches in molecular databases and QSAR analyses. An affinity fingerprint for a particular molecule is constructed as a vector of either its binding affinities, docking scores or superpositioning pseudo energies against a reference panel of proteins or small molecules. In contrast to most other molecular descriptors, affinity fingerprints are not directly derived from molecular structures. As such, they offer the possibility to detect similarities amongst molecules independent of their structural scaffolds. In this report we introduce the Flexsim-S method, an extension of our previous work on virtual affinity fingerprints. Moreover, we demonstrate that virtual affinity fingerprint methods are comparable to some popular two-dimensional descriptors in terms of correctly classifying compounds, but complementary with respect to the particular search results (hit lists).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Johnson, M.A. and Maggiora, G.M., Concepts and Applications of Molecular Similarity, Wiley, New York, NY, 1990.
Brown, R.D. and Martin, Y.C., J. Chem. Inf. Comput. Sci., 36 (1999) 572.
Patterson, D.E., Cramer, R.D., Ferguson, A.M., Clark, R.D. and Weinberger, L.E., J. Med. Chem., 39 (1996) 3049.
Matter, H., J. Med. Chem., 40 (1997) 1219.
Briem, H. and Kuntz, I.D., J. Med. Chem., 39 (1996) 3401.
DAYLIGHT, Version 4.62, DAYLIGHT Inc., Mission Viejo, CA.
ISIS, Version 2.1.4, Molecular Design Ltd., San Leandro, CA.
Weinstein, J.N., Kohn, K.W., Grever, M.R., Viswanadhan, V.N., Rubinstein, L.V., Monks, A.P., Scudiero, D.A., Welch, L., Koutsoukos, A.D., Chiausa, A.J. and Paull, K.D., Science, 258 (1992) 447.
Weinstein, J.N., Myers, T.G., O’Connor, P.M., Friend, S.H., Fornace, A.J., Kohn, K.W., Fojo, T., Bates, S.E., Rubinstein, L.V., Anderson, N.L., Buolamwini, J.K., van Osdol, W.W., Monks, A.P., Scudiero, D.A., Sausville, E.A., Zaharevitz, D.W., Bunow, B., Viswanadhan, V.N., Johnson, G.S., Wittes, R.E. and Paull, K.D., Science, 275 (1997) 343.
Kauvar, L.M., Higgins, D.L., Villar, H.O., Sportsman, J.R., Engqvist-Goldstein, A., Bukar, R., Bauer, K.E., Dilley, H. and Rocke, D.M., Chem. Biol., 2 (1995) 107.
Dixon, S.L. and Villar, H.O., J. Chem. Inf. Comput. Sci., 38 (1998) 1192.
DOCK, Version 3.5, University of California, San Francisco, CA.
Kuntz, I.D., Blaney, J.M., Oatley, S.J., Langridge, R. and Ferrin, T.E., J. Mol. Biol., 161 (1982) 269.
Shoichet, B.K., Bodian, D.L. and Kuntz, I.D., J. Comput. Chem., 13 (1992) 380.
Meng, E.C., Shoichet, B.K. and Kuntz, I.D., J. Comput. Chem., 13 (1992) 505.
Bernstein, F.C., Koetzle, T.F., Williams, G.J.B., Meyer Jr., E.F., Brice, M.D., Rodgers, J.R., Kennard, O., Shimanouchi, T. and Tasumi, M., J. Mol. Biol., 112 (1977) 535.
Lessel, U.F. and Briem, H., J. Chem. Inf. Comput. Sci., 40 (2000) 246.
Rarey, M., Kramer, B., Lengauer, T. and Klebe, G., J. Mol. Biol., 261 (1996) 470.
Ghuloum, A.M., Sage, C.R. and Jain, A.N., J. Med. Chem., 42 (1999) 1739.
Leo, A.J., Chem. Rev., 93 (1993) 1281.
Lemmen, C., Lengauer, T. and Klebe, G., J. Med. Chem., 41 (1998) 4502.
SUGAL Genetic Algorithm package, Version 2.1, written by Dr Andrew Hunter at the University of Sunderland, U.K.
Sadowski, J., Schwab, C.H. and Gasteiger, J., CORINA 3D-Structure Generator Program description, 1997.
Gasteiger, J. and Marsili, M., Tetrahedron, 36 (1980) 3219.
Lemmen, C., Hiller, C. and Lengauer, T., J. Comput.-Aided Mol. Design, 12 (1998) 491.
Rarey, M. and Dixon, J.S., J. Comput.-Aided Mol. Design, 12 (1998) 471. b. http://cartan.gmd.de/ftrees/ftrees_home.html.
SYBYL, Version 6.5.3, HQSAR Module, Tripos Inc., St. Louis, MO.
DOCK, Version 4.0, University of California, San Francisco, CA.
Ginn, C.M.R., Ranade, S.S., Willett, P. and Bradshaw, J., In: Arabnia, H.R. and Zhu, D. (Eds.) Proceedings of the International Conference on Multisource-Multisensor Information Fusion, Fusion’98, CSREA Press, 1998, pp. 307–313.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Kluwer Academic Publishers
About this chapter
Cite this chapter
Briem, H., Lessel, U.F. (2000). In vitro and in silico affinity fingerprints: Finding similarities beyond structural classes. In: Klebe, G. (eds) Virtual Screening: An Alternative or Complement to High Throughput Screening?., vol 20. Springer, Dordrecht. https://doi.org/10.1007/0-306-46883-2_13
Download citation
DOI: https://doi.org/10.1007/0-306-46883-2_13
Publisher Name: Springer, Dordrecht
Print ISBN: 978-0-7923-6633-1
Online ISBN: 978-0-306-46883-4
eBook Packages: Springer Book Archive