Abstract
The three-dimensional solution structures of proteins determinedwith NMR-derived constraints are almost always calculated in vacuo. Thesolution structure of (Ca2+)_2-calbindinD9k has been redetermined by new restrained molecular dynamics(MD) calculations that include Ca2+ ions and explicit solventmolecules. Four parallel sets of MD refinements were run to provide accuratecomparisons of structures produced in vacuo, in vacuo withCa2+ ions, and with two different protocols in a solvent bathwith Ca2+ ions. The structural ensembles were analyzed interms of structural definition, molecular energies, packing density,solvent-accessible surface, hydrogen bonds, and the coordination of calciumions in the two binding loops. Refinement including Ca2+ ionsand explicit solvent results in significant improvements in the precisionand accuracy of the structure, particularly in the binding loops. Theseresults are consistent with results previously obtained in free MDsimulations of proteins in solution and show that the rMD refinedNMR-derived solution structures of proteins, especially metalloproteins, canbe significantly improved by these strategies.
Similar content being viewed by others
References
Abagyan, R.A., Totrov, M.M. and Kuznetsov, D.N. (1994) J. Comput. Chem., 15, 488–506.
Ahlström, P., Teleman, O., Kördel, J., Forsén, S. and Jönsson, B. (1989) Biochemistry, 28, 3205–3211.
Berndt, K.D., Güntert, P. and Wüthrich, K. (1996) Proteins Struct. Funct. Genet., 24, 304–313.
Billeter, M., Qian, Y.Q., Otting, G., Müller, M., Gehring, W. and Wüthrich, K. (1990) J. Mol. Biol., 214, 183–197.
Billeter, M., Qian, Y.Q., Otting, G., Müller, M., Gehring, W. and Wüthrich, K. (1993) J. Mol. Biol., 234, 1084–1097.
Diamond, R. (1992) Protein Sci., 1, 1279–1287.
Gippert, G.P. (1996) Ph.D. Thesis, The Scripps Research Institute, La Jolla, CA, U.S.A.
Guenot, J. and Kollman, P.A. (1992) Protein Sci., 1, 1185–1205.
Havel, T. and Wüthrich, K. (1984) Bull. Math. Biol., 46, 674–698.
Havel, T. (1991) In Proteins: Structure, Dynamics and Design(Eds., Renugopalakrishnan, V., Carey, P.R., Smith, I.C.P., Huang, S.-G. and Storer, A.C.), ESCOM, Leiden, The Netherlands, pp. 110–115.
Kraulis, P.J. (1991) J. Appl. Crystallogr., 24, 946–950.
Kördel, J., Skelton, N.J., Akke, M., Palmer, A.G. and Chazin, W.J. (1992) Biochemistry, 31, 4856–4866.
Kördel, J., Skelton, N.J., Akke, M. and Chazin, W.J. (1993) J. Mol. Biol., 231, 711–734.
Laskowski, R.A., MacArthur, M.W., Moss, D.S. and Thornton, J.M. (1993) J. Appl. Crystallogr., 26, 283–291.
Lee, B. and Richards, F.M. (1971) J. Mol. Biol., 55, 379–400.
Levitt, M. and Sharon, R. (1988) Proc. Natl. Acad. Sci. USA, 85, 7557–7561.
Norin, M., Haeffner, F., Hult, K. and Edholm, O. (1994) Biophys. J., {vn67}, 548–559.
Pearlman, D.A., Case, D.A., Caldwell, J.C., Seibel, G.L., Singh, U.C., Weiner, P. and Kollman, P.A. (1991a) AMBER 4.0, University of California, San Francisco, CA, U.S.A.
Pearlman, D.A., Case, D.A. and Yip, P. (1991b) AMBER 4.0, University of California, San Francisco, CA, U.S.A.
Prompers, J.J., Folmer, F.H., Nilges, M., Folkers, P.J., Konings, R.N. and Hilbers, C.W. (1995) Eur. J. Biochem., 232, 506–514.
Shrake, A. and Rupley, J.A. (1973) J. Mol. Biol., 79, 351–371.
Skelton, N.J., Kördel, J., Akke, M. and Chazin, W.J. (1992) J. Mol. Biol., 227, 1100–1117.
Smith, L.J., Mark, A.E., Dobson, C.M. and van Gunsteren, W.F. (1995) Biochemistry, 34, 10918–10931.
Svensson, A., Thulin, E. and Forsén, S. (1992) J. Mol. Biol., 223, 601–606.
Szebenyi, D.M.E. and Moffat, K. (1986) J. Biol. Chem., 261, 8761–8777.
Torda, A.E., Scheek, R.M. and van Gunsteren, W.F. (1990) J. Mol. Biol., 214, 223–235.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kördel, J., Pearlman, D.A. & Chazin, W.J. Protein solution structure calculations in solution: Solvated molecular dynamics refinement of calbindin D9k . J Biomol NMR 10, 231–243 (1997). https://doi.org/10.1023/A:1018383102870
Issue Date:
DOI: https://doi.org/10.1023/A:1018383102870