Summary
Methods for the computation of free energies of solvation are reviewed, with emphasis on aqueous systems and discrete representation of the solvent molecules in Monte Carlo (MC) or molecular dynamics simulations. Precise results for small organic solutes can now be obtained routinely by MC/free energy perturbation calculations. The average error for computed free energies of hydration is 1.0 kcal/mol with the use of partial charges for the solutes from either OPLS unitedatom potential functions or from fitting to the electrostatic potential surface from 6-31G* ab initio calculations. A less rigorous, computationally more rapid method based on linear response theory is also found to be valuable and reduces the average error for the test set of 16 solutes to 0.6 kcal/mol.
Similar content being viewed by others
References
Warshel, A. and Chu, Z.T., In Cramer, C.J. and Truhlar, D.G. (Eds.) Structure and Reactivity in Aqueous Solution, ACS Symposium Series, Vol. 568, American Chemical Society, Washington, DC, 1994, p. 71.
Scheraga, H.A., ACS Symposium Series, Vol. 568, 1994, p. 360.
Tomasi, J. and Persico, M., Chem. Rev., 94 (1994) 2027.
Born, M., Z. Phys., 1 (1920) 45.
Onsager, L., J. Am. Chem. Soc., 58 (1936) 1486.
Still, W.C., Tempczyk, A., Hawley, R.C. and Hendrickson, T.F., J. Am. Chem. Soc., 112 (1990) 6127.
Jean-Charles, A., Nicholls, A., Sharp, K., Honig, B., Tempczyk, A., Hendrickson, T.F. and Still, W.C., J. Am. Chem. Soc., 113 (1991) 1454.
Cramer, C.J. and Truhlar, D.G., J. Comput.-Aided Mol. Design, 6 (1992) 629.
Tannor, D.J., Marten, B., Murphy, R., Friesner, R.A., Sitkoff, D., Nicholls, A., Ringnalda, M., Goddard III, W.A. and Honig, B., J. Am. Chem. Soc., 116 (1994) 11875.
Beveridge, D.L. and DiCapua, F.M., Annu. Rev. Biophys. Biophys. Chem., 18 (1989) 431.
Kollman, P., Chem. Rev., 93 (1993) 2395.
Jorgensen, W.L. and Ravimohan, C., J. Chem. Phys., 83 (1985) 3050.
Severance, D.L. and Jorgensen, W.L., ACS Symposium Series, Vol. 568, 1994, p. 243.
Meng, E.C., Cieplak, P., Caldwell, J.W. and Kollman, P.A., J. Am. Chem. Soc., 116 (1994) 12061.
Field, M.J., Bash, P.A. and Karplus, M., J. Comput. Chem., 11 (1990) 700.
Gao, J. and Xia, X., Science, 258 (1992) 631.
Jorgensen, W.L., Blake, J.F. and Buckner, J.K., Chem. Phys., 129 (1989) 193.
Zwanzig, R.W., J. Chem. Phys., 22 (1954) 1420.
Severance, D.L., Essex, J.W. and Jorgensen, W.L., J. Comput. Chem., 16 (1995) 311.
Mezei, M., J. Chem. Phys., 86 (1987) 7084.
Tirado-Rives, J., Maxwell, D.S. and Jorgensen, W.L., J. Am. Chem. Soc., 115 (1993) 11590.
Mitchell, M.J. and McCammon, J.A., J. Comput. Chem., 12 (1991) 271.
Jorgensen, W.L., BOSS v. 3.5, Yale University, New Haven, CT, 1994.
Van Gunsteren, W.F. and Berendsen, H.J.C., Angew. Chem., Int. Ed. Engl., 29 (1990) 992.
Jorgensen, W.L. and Briggs, J.M., J. Am. Chem. Soc., 111 (1989) 4190.
Jorgensen, W.L., Briggs, J.M. and Contreras, M.L., J. Phys. Chem., 94 (1990) 1683.
Jorgensen, W.L. and Severance, D.L., J. Am. Chem. Soc., 112 (1990) 4768.
Jorgensen, W.L. and Nguyen, T.B., J. Comput. Chem., 14 (1993) 195.
Carlson, H.A., Nguyen, T.B., Orozco, M. and Jorgensen, W.L., J. Comput. Chem., 14 (1993) 1240.
Orozco, M., Jorgensen, W.L. and Luque, F.J., J. Comput. Chem., 14 (1993) 1498.
Duffy, E.M., Severance, D.L. and Jorgensen, W.L., Isr. J. Chem., 33 (1993) 323.
Kaminski, G., Duffy, E.M., Matsui, T. and Jorgensen, W.L., J. Phys. Chem., 98 (1994) 13077.
Jorgensen, W.L., Chandrasekhar, J., Madura, J.D., Impey, R.W. and Klein, M.L., J. Chem. Phys., 79 (1983) 926.
Jorgensen, W.L. and Madura, J.D., Mol. Phys., 99 (1985) 1381.
Berendsen, H.J.C., Postma, J.P.M., Van Gunsteren, W.F. and Hermans, J., In Pullman, B. (Ed.) Intermolecular Forces, Reidel, Dordrecht, 1981, pp. 331–342.
Jorgensen, W.L., J. Am. Chem. Soc., 103 (1981) 335.
Stillinger, F.H. and Rahman, A., J. Chem. Phys., 60 (1974) 1545.
Neumann, M., J. Chem. Phys., 85 (1986) 1567.
Hermans, J., Pathiaseril, A. and Anderson, A., J. Am. Chem. Soc., 110 (1988) 5982.
Ferrario, M. and Tani, A., Chem. Phys. Lett., 121 (1985) 182.
Alper, H.E. and Levy, R.M., J. Chem. Phys., 91 (1989) 1242.
Belhadj, M., Alper, H.E. and Levy, R.M., Chem. Phys. Lett., 179 (1991) 13.
Berendsen, H.J.C., Grigera, J.R. and Straatsma, T.P., J. Phys. Chem., 91 (1987) 6269.
Reddy, M.R. and Berkowitz, M., Chem. Phys. Lett., 155 (1989) 173.
Soper, A.K. and Phillips, M.G., Chem. Phys., 107 (1986) 47.
Sprik, M. and Klein, M.L., J. Chem. Phys., 89 (1988) 7556.
Kuwajima, S. and Warshel, A., J. Phys. Chem., 94 (1990) 460.
Dang, L.X., Rice, J.E., Caldwell, J. and Kollman, P.A., J. Am. Chem. Soc., 113 (1991) 2481.
Straatsma, T.P. and McCammon, J.A., Chem. Phys. Lett., 177 (1991) 433.
Jorgensen, W.L. and Severance, D.L., J. Chem. Phys., 99 (1993) 4233.
Åqvist, J., J. Phys. Chem., 94 (1990) 8021.
See for example: Reimers, J.R., Watts, R.O. and Klein, M.L., J. Chem. Phys., 64 (1992) 95.
Cieplak, P., Kollman, P. and Lybrand, T., J. Chem. Phys., 92 (1990) 6755.
Briggs, J.M., Matsui, T. and Jorgensen, W.L., J. Comput. Chem., 11 (1990) 958.
Hine, J. and Mookerjee, P.K., J. Org. Chem., 40 (1975) 292.
Ben-Naim, A. and Marcus, Y., J. Chem. Phys., 81 (1984) 2016.
Wolfenden, R., Andersson, L., Cullis, P.M. and Southgate, C.C.B., Biochemistry, 20 (1981) 849.
Wolfenden, R., Biochemistry, 17 (1978) 201.
Carlson, H.A. and Jorgensen, W.L., J. Phys. Chem., 99 (1995) 10667.
Jorgensen, W.L., Maxwell, D.S. and Tirado-Rives, J., unpublished results.
Morgantini, P.-Y. and Kollman, P.A., J. Am. Chem. Soc., 117 (1995) 6057.
Ding, Y., Bernardo, D.N., Krogh-Jespersen, K. and Levy, R.M., manuscript submitted for publication.
Jorgensen, W.L. and Swenson, C.J., J. Am. Chem. Soc., 107 (1985) 569.
Cornell, W.D., Cieplak, P., Bayly, C.I. and Kollman, P.A., J. Am. Chem. Soc., 115 (1993) 9620.
Åqvist, J., Medina, C. and Sammuelsson, J.-E., Protein Eng., 7 (1994) 385.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jorgensen, W.L., Tirado-Rives, J. Free energies of hydration for organic molecules from Monte Carlo simulations. Perspectives in Drug Discovery and Design 3, 123–138 (1995). https://doi.org/10.1007/BF02174470
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02174470