Abstract
Introducing experimental values as restraints into molecular dynamics (MD) simulations to bias the values of particular molecular properties, such as nuclear Overhauser effect intensities or distances, 3J coupling constants, chemical shifts or crystallographic structure factors, towards experimental values is a widely used structure refinement method. To account for the averaging of experimentally derived quantities inherent in the experimental techniques, time-averaging restraining methods may be used. In the case of structure refinement using 3J coupling constants from NMR experiments, time-averaging methods previously proposed can suffer from large artificially induced structural fluctuations. A modified time-averaged restraining potential energy function is proposed which overcomes this problem. The different possible approaches are compared using stochastic dynamics simulations of antamanide, a cyclic peptide of ten residues.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Brüschweiler, R., Blackledge, M. and Ernst, R.R. (1991) J. Biomol. NMR, 1, 3-11.
Bystrov, V.F. (1976) Prog. NMR Spectrosc., 10, 41-81.
Karle, I.L., Wieland, T., Schermer, D. and Ottenheym, H.C.J. (1979) Proc. Natl. Acad. Sci. USA, 76 1532-1536.
Karplus, M. (1959) J. Chem. Phys., 30, 11-15.
Kessler, H., Bats, J.W., Lautz, J. and Müller, A. (1989) Liebigs Ann. Chem., 9, 913-928.
Kessler, H., Griesinger, C., Lautz, J., Müller, A., van Gunsteren, W.F. and Berendsen, H.J.C. (1988) J. Am. Chem. Soc., 110, 3393-3396.
Nanzer, A.P., Torda, A.E., Bisang, C., Weber, C., Robinson, J.A. and van Gunsteren, W.F. (1997) J. Mol. Biol., 267, 1012-1025.
Pardi, A., Billeter, M. and Wüthrich, K. (1984) J. Mol. Biol., 180, 741-751.
Pearlman, D.A. (1994) J. Biomol. NMR, 4, 279-299.
Ryckaert, J.-P., Ciccotti, G. and Berendsen, H.J.C. (1977) J. Comput. Phys., 23, 327-341.
Schiffer, C.A., Gros, P. and van Gunsteren, W.F. (1995) Acta Cryst., D51, 85-92.
Scott, W.R.P., Hünenberger, P.H., Tironi, I.G., Mark, A.E., Billeter, S.R., Fennen, J., Torda, A.E., Huber, T., Krüger, P. and van Gunsteren, W.F. (1998) J. Phys. Chem. A. to be submitted.
Torda, A.E., Brunne, R.M., Huber, T., Kessler, H. and van Gunsteren, W.F. (1993) J. Biomol. NMR, 3, 55-66.
Torda, A.E., Scheek, R.M. and van Gunsteren, W.F. (1990) J. Mol. Biol., 214, 223-235.
van Gunsteren, W.F. and Berendsen, H.J.C. (1988) Mol. Simul., 1, 173-185.
van Gunsteren, W.F., Billeter, S.R., Eising, A.A., Hünenberger, P.H., Krüger, P., Mark, A.E., Scott, W.R.P. and Tironi, I.G. (1996) Biomolecular Simulation: The GROMOS96 Manual and User Guide. VdF: Hochschulverlag AG an der ETH Zürich and BIOMOS b.v., Zürich, Groningen.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Scott, W.R., Mark, A.E. & van Gunsteren, W.F. On using time-averaging restraints in molecular dynamics simulation. J Biomol NMR 12, 501–508 (1998). https://doi.org/10.1023/A:1008306732538
Issue Date:
DOI: https://doi.org/10.1023/A:1008306732538