Summary
A new method, a restrained Monte Carlo (rMC) calculation, is demonstrated for generating high-resolution structures of DNA oligonucleotides in solution from interproton distance restraints and bounds derived from complete relaxation matrix analysis of two-dimensional nuclear Overhauser effect (NOE) spectral peak intensities. As in the case of restrained molecular dynamics (rMD) refinement of structures, the experimental distance restraints and bounds are incorporated as a pseudo-energy term (or penalty function) into the mathematical expression for the molecular energy. However, the use of generalized helical parameters, rather than Cartesian coordinates, to define DNA conformation increases efficiency by decreasing by an order of magnitude the number of parameters needed to describe a conformation and by simplifying the potential energy profile. The Metropolis Monte Carlo method is employed to simulate an annealing process. The rMC method was applied to experimental 2D NOE data from the octamer duplex d(GTA-TAATG)·d(CATTATAC). Using starting structures from different locations in conformational space (e.g. A-DNA and B-DNA), the rMC calculations readily converged, with a root-mean-square deviation (RMSD) of <0.3 Å between structures generated using different protocols and starting structures. Theoretical 2D NOE peak intensities were calculated for the rMC-generated structures using the complete relaxation matrix program CORMA, enabling a comparison with experimental intensities via residual indices. Simulation of the vicinal proton coupling constants was carried out for the structures generated, enabling a comparison with the experimental deoxyribose ring coupling constants, which were not utilized in the structure determination in the case of the rMC simulations. Agreement with experimental 2D NOE and scalar coupling data was good in all cases. The rMC structures are quite similar to that refined by a traditional restrained MD approach (RMSD<0.5 Å) despite the different force fields used and despite the fact that MD refinement was conducted with additional restraints imposed on the endocyclic torsion angles of deoxyriboses. The computational time required for the rMC and rMD calculations is about the same. A comparison of structural parameters is made and some limitations of both methods are discussed with regard to the average nature of the experimental restraints used in the refinement.
Similar content being viewed by others
Abbreviations
- MC:
-
Monte Carlo
- rMC:
-
restrained Monte Carlo
- MD:
-
molecular dynamics
- rMD:
-
restrained molecular dynamics
- DG:
-
distance geometry
- EM:
-
energy minimization
- 2D NOE:
-
two-dimensional nuclear Overhauser effect
- DQF-COSY:
-
double-quantum-filtered correlation spectroscopy
- RMSD:
-
root-mean-square deviation
References
Altona, C. and Sundaralingam, M. (1972) J. Am. Chem. Soc., 94, 8205–8212.
Baleja, J.D., Pon, R.T. and Sykes, B.D. (1990) Biochemistry, 29, 4828–4839.
Borgias, B.A. and James, T.L. (1988) J. Magn. Reson., 79, 493–512.
Borgias, B.A. and James, T.L. (1989) Methods Enzymol., 176, 169–183.
Borgias, B.A. and James, T.L. (1990) J. Magn. Reson., 87, 475–487.
Braun, W. (1987) Q. Rev. Biophys., 19, 115–157.
Brünger, A.T. and Karplus, M. (1991) Acc. Chem. Res., 24, 54–61.
Chuprina, V.P., Khutorskii, V.E. and Poltev, V.I. (1981) Stud. Biophys., 85, 81–88.
De Leeuw, F.A.A.M., Van Beuzekom, A. and Altona, C. (1983) J. Comp. Chem., 4, 438–448.
Dickerson, R.E., Bansal, M., Calladine, C.R., Diekmann, S., Hunter, W.N., Kennard, O., Lavery, R., Nelson, H.J.C., Saenger, W., Shakked, Z., Sklenar, H., Soumpasis, D.M., Von Kitzing, E., Wang, A.-H.-J. and Zhurkin, V.B. (1989) EMBO J., 8, 1–4.
Gorin, A.A., Ulyanov, N.B. and Zhurkin, V.B. (1990) Molek. Biol. (Eng. transl.), 24, 1036–1047.
Gupta, G., Bansal, M. and Sasisekharan, V. (1980) Proc. Natl. Acad. Sci. USA, 77, 6486–6490.
Haasnoot, C.A.G., De Leeuw, F.A.A.M. and Altona, C. (1980) Tetrahedron, 36, 2783–2792.
Havel, T.F., Kuntz, I.D. and Crippen, G.M. (1983) Bull. Math. Biol., 45, 665–720.
James, T.L. (1991) Curr. Opin. Struct. Biol., 1, 1042–1053.
James, T.L., Gochin, M., Kerwood, D.J., Pearlman, D.A., Schmitz, U. and Thomas, P.D. (1991) In Computational Aspects of the Study of Biological Macromolecules by Nuclear Magnetic Resonance Spectroscopy (Eds, Hoch, J.C., Poulsen, F.M. and Redfield, C.) Plenum Press, New York, pp. 331–347.
Keepers, J.W. and James, T.L. (1984) J. Magn. Reson., 57, 404–426.
Kerwood, D.J., Zon, G. and James, T.L. (1991) Eur. J. Biochem., 197, 583–595.
Kim, S.-G. and Reid, B.R. (1992) Biochemistry, 31, 12103–12116.
Kumar, A., James, T.L. and Levy, G.C. (1992) Isr. J. Chem., 32, 257–261.
Lavery, R. (1988) In DNA Bending and Curvature (Eds, Olson, W.K., Sarma, M.H., Sarma, R.H. and Sundaralingam, M.) Vol. 3, Adenine Press, New York, pp. 191–211.
Levy, R.M., Bassolino, D.A., Kitchen, D.B. and Pardi, A. (1989) Biochemistry, 28, 9361–9372.
Liu, H., Thomas, P.D. and James, T.L. (1992) J. Magn. Reson., 98, 163–175.
Mauffret, O., Hartmann, B., Convert, O., Lavery, R. and Fermandjian, S. (1992) J. Mol. Biol., 227, 852–875.
McCammon, J.A. and Harvey, S.C. (1987) Dynamics of Proteins and Nucleic Acids, Cambridge University Press, Cambridge.
Metropolis, N.A., Rosenbluth, A.M., Rosenbluth, M.N., Teller, A.H. and Teller, E. (1953) J. Chem. Phys., 21, 1087–1092.
Mujeeb, A., Kerwin, S.M., Egan, W., Kenyon, G.L. and James, T.L. (1992) Biochemistry, 31, 9325–9338.
Nikonowicz, E. and Gorenstein, D.G. (1992) J. Am. Chem. Soc., 114, 7494–7503.
Nilges, M., Clore, G.M., Gronenborn, A., Piel, N. and McLaughlin, L.W. (1987) Biochemistry, 26, 3734–3744.
Nilsson, L., Clore, G.M., Gronenborn, A., Brünger, A.T. and Karplus, M. (1986) J. Mol. Biol., 188, 455–475.
Olson, W.K. (1977) Proc. Natl. Acad. Sci. USA, 74, 1775–1779.
Oshiro, C.M., Thomason, J.F. and Kuntz, I.D. (1991) Biopolymers, 31, 1049–1064.
Pearlman, D.A. and Kollman, P.A. (1991) J. Mol. Biol., 220, 457–479.
Pearlman, D.A., Case, D.A., Caldwell, J., Seibel, G.L., Singh, U.C., Weiner, P.K. and Kollman, P.A. (1991) AMBER 4.0, University of California, San Francisco.
Poltev, V.I. and Shulyupina, N.V. (1986) J. Biomol. Struct. Dyn., 3, 739–765.
Ripoll, D.R. and Ni, F. (1992) Biopolymers, 32, 359–365.
Ryckaert, J.P., Cicotti, G. and Berendsen, H.J.C. (1977) J. Comp. Phys., 23, 327–341.
Schmitz, U., Kumar, A. and James, T.L. (1992a) J. Am. Chem. Soc., 114, 10654–10656.
Schmitz, U., Sethson, I., Egan, W. and James, T.L. (1992b) J. Mol. Biol., 227, 510–531.
Schmitz, U., Ulyanov, N.B., Kumar, A. and James, T.L. (1993) J. Mol. Biol., in press.
Stolarski, R., Egan, W. and James, T.L. (1992) Biochemistry, 31, 7027–7042.
Thomas, P.D., Basus, V.J. and James, T.L. (1991) Proc. Natl. Acad. Sci. USA, 88, 1237–1241.
Torda, A.E., Scheek, R.M. and Van Gunsteren, W.F. (1990) J. Mol. Biol., 214, 223–235.
Ulyanov, N.B. and Zhurkin, V.B. (1982) Molek. Biol. (Eng. transl.), 16, 857–867.
Ulyanov, N.B. and Zhurkin, V.B. (1984) J. Biomol. Struct. Dyn., 2, 361–385.
Ulyanov, N.B., Gorin, A.A. and Zhurkin, V.B. (1989) In Proc. Int. conf. Supercomp. '89: Supercomputer Applications (Eds, Kartashev, L.P. and Kartashev, S.I.) Int. Supercomputing Inst., Inc., St. Petersburg, Florida, pp. 368–370.
Ulyanov, N., Gorin, A.A., Zhurkin, V.B., Chen, B.-C., Sarma, M.H. and Sarma, R.H. (1992) Biochemistry, 31, 3918–3930.
Van Gunsteren, W.F., Boelens, R., Kaptein, R. and Zuiderweg, E.R.P. (1983) In Nucleic Acid Conformation and Dynamics, NATO/CECAM Workshop Report (Ed. Olson, W.K.) Orsay, pp. 79–82.
Weisz, K., Shafer, R.H., Egan, W. and James, T.L. (1992) Biochemistry, 31, 7477–7487.
Zhurkin, V.B., Lysov, Y.P. and Ivanov, V.I. (1978) Biopolymers, 17, 377–412.
Zhurkin, V.B., Poltev, V.I. and Florentiev, V.L. (1981) Molek. Biol. (Eng. transl.), 14, 882–895.
Zhurkin, V.B., Ulyanov, N.B., Gorin, A.A. and Jernigan, R.L. (1991) Proc. Natl. Acad. Sci. USA, 88, 7046–7050.
Author information
Authors and Affiliations
Additional information
To whom correspondence should be addressed.
Rights and permissions
About this article
Cite this article
Ulyanov, N.B., Schmitz, U. & James, T.L. Metropolis Monte Carlo calculations of DNA structure using internal coordinates and NMR distance restraints: An alternative method for generating a high-resolution solution structure. J Biomol NMR 3, 547–568 (1993). https://doi.org/10.1007/BF00174609
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00174609