Summary
A new computational and graphical method for facilitating ligand-protein docking studies is developed on a three-dimensional computer graphics display. Various physical and chemical properties inside the ligand binding pocket of a receptor protein, whose structure is elucidated by X-ray crystal analysis, are calculated on three-dimensional grid points and are stored in advance. By utilizing those tabulated data, it is possible to estimate the non-bonded and electrostatic interaction energy and the number of possible hydrogen bonds between protein and ligand molecules in real time during an interactive docking operation. The method also provides a comprehensive visualization of the local environment inside the binding pocket.
With this method, it becomes easier to find a roughly stable geometry of ligand molecules, and one can therefore make a rapid survey of the binding capability of many drug candidates. The method will be useful for drug design as well as for the examination of protein-ligand interactions.
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Smith, R.N., Hansch, C., Kim, K.H., Omiya, B., Fukumura, G., Selassie, C.D., Jow, P.Y.C., Blaney, J.M. and Langridge, R., Arch. Biochem. Biophys., 215 (1982) 319–328.
Smith, G.M., Hangauer, D.G., Andose, J.D., Bush, B.L., Fluder, E.M., Gund, P. and McIntyre, E.F., Drug Inf. J., 18 (1984) 167–178.
Blaney, J.M., Weiner, P.K., Dearing, A., Kollman, P.A., Jorgensen, E.C., Oatley, S.J., Burridge, J.M. and Blake, C.C.F., J.Am.Chem.Soc., 104 (1982) 6424–6434.
Freudenreich, C., Samama, J.-P. and Biellmann, J.-F., J.Am.Chem.Soc., 106 (1984) 3344–3353.
Weiner, P.K., Langridge, R., Blaney, J.M., Schaefer, R. and Kollman, P.A., Proc. Natl.Acad.Sci. USA, 79 (1982) 3754–3758.
Blaney, J.M., Jorgensen, E.C., Connolly, M.L., Ferrin, T.E., Langridge, R., Oatley, S.J., Burridge, J.M. and Blake, C.C.F., J.Med.Chem., 25 (1982) 785–790.
Itai, A. and Tomioka, N., Abstracts of Papers, 6th Symposium on Medicinal Chemistry, Pharmaceutical Society of Japan, Tokyo, 1984, p. 105.
Tomioka, N., Itai, A. and Iitaka, Y., In Iitaka, Y. and Itai, A. (Eds.) Proceedings of the Symposium on Three-Dimensional Structures and Drug Design, Univ. Tokyo Press, 1987, pp. 186–194.
Goodford, P.J., J. Med.Chem., 28 (1985) 849–857.
Weiner, P.K. and Kollman, P.A., J.Comp.Chem., 2 (1981) 287–303.
Brooks, B.R., Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaminathan, S. and Karplus, M., J.Comp.Chem., 4 (1983) 187–217.
Weiner, S.J., Kollman, P.A., Case, D.A., Singh, U.C., Ghio, C., Alagona, G., Profeta, S., Jr. and Weiner, P., J.Am.Chem.Soc., 106 (1984) 765–784.
Warshel, A., J.Phys.Chem., 83 (1979) 1640–1652.
McCammon, J.A., Wolynes, P.G. and Karplus, M., Biochemistry, 18 (1979) 927–942.
Kollman, P.A., Weiner, P.K. and Dearing, A., Biopolymers, 20 (1981) 2583–2621.
Murray-Rust, P. and Glusker, J.P., J.Am.Chem.Soc., 106 (1984) 1018–1025.
Vedani, A. and Dunitz, J.D., J.Am.Chem.Soc., 107 (1985) 7653–7658.
Hansch, C., Li, R., Blaney, J.M. and Langridge, R., J.Med.Chem., 25 (1982) 777–784.
Kuyper, L.F., Roth, B., Baccanari, D.P., Ferone, R., Beddell, C.R., Champness, J.N., Stammers, D.K., Dann, J.G., Norrington, F.E.A., Baker, D.J. and Goodford, P.J., J.Med.Chem., 25 (1982) 1120–1122.
Ghose, A.K. and Crippen, G.M., J.Med.Chem., 27 (1984) 901–914.
Bolin, J.T., Filman, D.J., Matthews, D.A., Hamlin, R.C. and Kraut, J., J.Biol. Chem., 257 (1982) 13650–13662.
Matthews, D.A., Bolin, J.T., Burridge, J.M., Filman, D.J., Volz, K.W. and Kraut, J., J.Biol.Chem., 260 (1985) 392–399.
Koetzle, T.F. and Williams, G.J.B., J.Am.Chem.Soc., 98 (1976) 2074–2078.
Kosugi, N. and Kuroda, H., Chem.Phys.Lett., 74 (1980) 490–493.
Matthews, D.A., Bolin, J.T., Burridge, J.M., Filman, D.J. Volz, K.W., Kaufman, B.T., Beddell, C.R., Champness, J.N., Stammers, D.K. and Kraut, J., J. Biol.Chem., 260 (1985) 381–391.
Busetta, B., Tickle, I.J. and Blundell, T.L., J.Appl.Cryst., 16 (1983) 432–437.
Pattabiraman, N., Levitt, M., Ferrin, T.E. and Langridge, R., J.Comp.Chem., 6 (1985) 432–436.
Lippincott, E.R. and Schroeder, R., J.Chem.Phys., 23 (1955) 1099–1106.
Chidambaram, R., Balasubramanian, R. and Ramachandran, G.N., Biochim.Biophys.Acta. 221 (1970) 182–195.
Huber, R., Kukla, D., Bode, W., Schwager, P., Bartels, K., Deisenhofer, J. and Steigemann, W., J.Mol.Biol., 89 (1974) 73–101.
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Tomioka, N., Itai, A. & Iitaka, Y. A method for fast energy estimation and visualization of protein-ligand interaction. J Computer-Aided Mol Des 1, 197–210 (1987). https://doi.org/10.1007/BF01677044
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DOI: https://doi.org/10.1007/BF01677044