Abstract
Accurate computation of protein-ligand binding affinities is a challenging goal with great potential value in the design of therapeutic agents. Applications of statistical mechanics simulations to the problem are considered that feature full atomic-level descriptions of the protein, ligand and aqueous environment. Basic concepts on the methodology and intermolecular interactions in solution are presented along with results of Monte Carlo simulations for binding of inhibitors by trypsin and thrombin.
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References
Lybrand, T. P. (1995) Curr. Opin. Struct. Biol. 5, 224.
Verlinde, C. L. M. J. and Hol, W. G. H. (1994) Structure 2, 577.
Jorgensen, W. L. (1991) Chemtracts - Org. Chem. 4,91.
Kollman, P. A. (1993) Chem. Rev. 93, 2395.
Jorgensen, W. L. and Tirado-Rives, J. (1996) J. Phys. Chem. 100, 14508.
See, for example: Jorgensen, W. L. and Nguyen, T. B. (1993) Proc. Natl. Acad. Sci. USA 90, 1194. Duffy, E. M. and Jorgensen, W. L. (1994) J. Am. Chem. Soc. 116, 6337.
Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. and Klein, M. L. (1983) J. Chem. Phys. 79, 926.
Jorgensen, W. L. and Tirado-Rives, J. (1988) J. Am. Chem. Soc. 110, 1657.
Jorgensen, W. L. and Severance, D. L. (1990) J. Am. Chem. Soc. 112,4768.
Jorgensen, W. L., Maxwell, D. S. and Tirado-Rives, J. (1996) J. Am. Chem. Soc. 118,0000.
Ã…qvist, J., Medina, C. and Sammuelsson, J.-E. (1994) Protein Eng. 7, 385.
Ã…qvist, J. and Mowbray, S. M. (1995) J. Biol. Chem. 270,9978.
Hansson, T. and Ã…qvist, J. (1995) Protein Eng. 8, 1137.
Carlson, H. A. and Jorgensen, W. L. (1995) J. Phys. Chem. 99,10667.
Paulsen, M. D. and Ornstein, R. L. (1996) Protein Eng. 9, 567.
Jones-Hertzog, D. K. and Jorgensen, W. L., submitted for publication.
Jorgensen, W. L. (1995) BOSS, Version 3.6; Yale University; New Haven, CT.
Jorgensen, W. L. (1996) MCPRO, Version 1.4; Yale University; New Haven,CT.
Frisch, M. J., Trucks, G. W., Head-Gordon, M., Gill, P. M. W., Wong, M. W., Foresman, J. B., Johnson, B. G., Schelgal, H. B., Robb, M. A., Replogle, E. S., Gomperts, R., Andres, J. L., Raghavachari, K., Binkley, J. S., Gonzalez, C., Martin, R. L., Fox, D. J., Defrees, D. J., Baker, J., Stewart, J. J. P. and Pople, J. A. (1994) Gaussian94, Revision A; Gaussian, Inc.; Pittsburgh, PA.
Jorgensen, W. L., Briggs, J. M. and M. L. Contreras (1990) J. Phys. Chem. 94,1683.
Marquart, M., Walter, J., Deisenhofer, J., Bode, W. and Huber, R. (1983) Acta Cryst. B 39,480.
Banner, D. W. and Hadvary, P. (1991) J. Biol. Chem. 266, 20085.
Jorgensen, W. L. (1989) J. Am. Chem. Soc. 111, 3770.
Krikorian, S. E. (1982) J. Phys. Chem. 86, 1875. Klotz, I. M. and Franzen, J. S. (1962) J. Am. Chem. Soc. 84, 3461.
Blokzijl, W. and Engberts, J. B. F. N. (1993) Angew. Chem. Int. Ed. Engl. 32,1545.
Weber, P. C., Wendoloski, J. J., Pantoliano, M. W. and Salenum, F. R. (1992) J. Am. Chem. Soc. 114,3197.
Mares-Guia, M., Nelson, D. L. and Rogana, E. (1977) J. Am. Chem. Soc. 99,2331.
Kikumoto, R., Tamao, Y., Teauka, T., Tonomura, S., Hara, H. and Ninomiya, K. (1984) Biochemistry 23, 85.
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Jorgensen, W.L. et al. (1997). Approaches to Protein-Ligand Binding from Computer Simulations. In: Vergoten, G., Theophanides, T. (eds) Biomolecular Structure and Dynamics. NATO ASI Series, vol 342. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5484-0_2
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DOI: https://doi.org/10.1007/978-94-011-5484-0_2
Publisher Name: Springer, Dordrecht
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