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. 1997 Oct 1;25(19):3855–3862. doi: 10.1093/nar/25.19.3855

Sensitivity of NMR internucleotide distances to B-DNA conformation: underlying mechanics.

A Lefebvre 1, S Fermandjian 1, B Hartmann 1
PMCID: PMC146986  PMID: 9380508

Abstract

Nuclear magnetic resonance (NMR) spectroscopy, combining correlated spectroscopy (COSY) coupling constant measurements with nuclear Overhauser effect spectroscopy (NOESY) interatomic distances, should make it possible to determine an averaged solution structure for DNA oligomers. However, even if such data could be obtained with high accuracy, it is not clear which structural parameters of DNA would be determined. Here, the relationships between measurable internucleotide distances and helical parameters are systematically studied through molecular modelling. Investigations are carried out using four representative sequences, (ACGT)n, (TCGA)n, (AGCT)n and (TGCA)n, composed of repeated tetranucleotides belonging to oligomers previously studied by NMR. Correlations between interatomic distances become evident and strong connections between distances and inter-base helical parameters are observed. Results imply that twist, roll, shift and slide values can be accurately determined from NMR data. Sequence independent mechanical coupling which link backbone and sugar conformations to helical twist are also described.

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Selected References

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  1. Boutonnet N., Hui X., Zakrzewska K. Looking into the grooves of DNA. Biopolymers. 1993 Mar;33(3):479–490. doi: 10.1002/bip.360330314. [DOI] [PubMed] [Google Scholar]
  2. Conte M. R., Bauer C. J., Lane A. N. Determination of sugar conformations by NMR in larger DNA duplexes using both dipolar and scalar data: application to d(CATGTGACGTCACATG)2. J Biomol NMR. 1996 May;7(3):190–206. doi: 10.1007/BF00202036. [DOI] [PubMed] [Google Scholar]
  3. Definitions and nomenclature of nucleic acid structure parameters. J Mol Biol. 1989 Feb 20;205(4):787–791. doi: 10.1016/0022-2836(89)90324-0. [DOI] [PubMed] [Google Scholar]
  4. Fedoroff OYu, Reid B. R., Chuprina V. P. Sequence dependence of DNA structure in solution. J Mol Biol. 1994 Jan 7;235(1):325–330. doi: 10.1016/s0022-2836(05)80036-1. [DOI] [PubMed] [Google Scholar]
  5. Gaudin F., Paquet F., Chanteloup L., Beau J. M., Nguyen T. T., Lancelot G. Selectively 13C-enriched DNA: dynamics of the C1'-H1' vector in d(CGCAAATTTGCG)2. J Biomol NMR. 1995 Jan;5(1):49–58. doi: 10.1007/BF00227469. [DOI] [PubMed] [Google Scholar]
  6. Gorin A. A., Zhurkin V. B., Olson W. K. B-DNA twisting correlates with base-pair morphology. J Mol Biol. 1995 Mar 17;247(1):34–48. doi: 10.1006/jmbi.1994.0120. [DOI] [PubMed] [Google Scholar]
  7. Grzeskowiak K., Yanagi K., Privé G. G., Dickerson R. E. The structure of B-helical C-G-A-T-C-G-A-T-C-G and comparison with C-C-A-A-C-G-T-T-G-G. The effect of base pair reversals. J Biol Chem. 1991 May 15;266(14):8861–8883. doi: 10.2210/pdb1d23/pdb. [DOI] [PubMed] [Google Scholar]
  8. Hahn M., Heinemann U. DNA helix structure and refinement algorithm: comparison of models for d(CCAGGCm5CTGG) derived from NUCLSQ, TNT and X-PLOR. Acta Crystallogr D Biol Crystallogr. 1993 Sep 1;49(Pt 5):468–477. doi: 10.1107/S0907444993004858. [DOI] [PubMed] [Google Scholar]
  9. Hartmann B., Piazzola D., Lavery R. BI-BII transitions in B-DNA. Nucleic Acids Res. 1993 Feb 11;21(3):561–568. doi: 10.1093/nar/21.3.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Heinemann U., Alings C. Crystallographic study of one turn of G/C-rich B-DNA. J Mol Biol. 1989 Nov 20;210(2):369–381. doi: 10.1016/0022-2836(89)90337-9. [DOI] [PubMed] [Google Scholar]
  11. Heinemann U., Hahn M. C-C-A-G-G-C-m5C-T-G-G. Helical fine structure, hydration, and comparison with C-C-A-G-G-C-C-T-G-G. J Biol Chem. 1992 Apr 15;267(11):7332–7341. [PubMed] [Google Scholar]
  12. Kaluarachchi K., Meadows R. P., Gorenstein D. G. How accurately can oligonucleotide structures be determined from the hybrid relaxation rate matrix/NOESY distance restrained molecular dynamics approach? Biochemistry. 1991 Sep 10;30(36):8785–8797. doi: 10.1021/bi00100a009. [DOI] [PubMed] [Google Scholar]
  13. Kim S. G., Lin L. J., Reid B. R. Determination of nucleic acid backbone conformation by 1H NMR. Biochemistry. 1992 Apr 14;31(14):3564–3574. doi: 10.1021/bi00129a003. [DOI] [PubMed] [Google Scholar]
  14. Kim S. G., Reid B. R. Solution structure of the TnAn DNA duplex GCCGTTAACGCG containing the HpaI restriction site. Biochemistry. 1992 Dec 8;31(48):12103–12116. doi: 10.1021/bi00163a020. [DOI] [PubMed] [Google Scholar]
  15. Lane A. N. Solution conformations of d(CGTACG)2 determined from NMR experiments. Biochim Biophys Acta. 1990 Jun 21;1049(2):205–212. doi: 10.1016/0167-4781(90)90041-y. [DOI] [PubMed] [Google Scholar]
  16. Lavery R., Hartmann B. Modelling DNA conformational mechanics. Biophys Chem. 1994 May;50(1-2):33–45. doi: 10.1016/0301-4622(94)85018-6. [DOI] [PubMed] [Google Scholar]
  17. Lavery R., Sklenar H. Defining the structure of irregular nucleic acids: conventions and principles. J Biomol Struct Dyn. 1989 Feb;6(4):655–667. doi: 10.1080/07391102.1989.10507728. [DOI] [PubMed] [Google Scholar]
  18. Lefebvre A., Mauffret O., Hartmann B., Lescot E., Fermandjian S. Structural behavior of the CpG step in two related oligonucleotides reflects its malleability in solution. Biochemistry. 1995 Sep 19;34(37):12019–12028. doi: 10.1021/bi00037a045. [DOI] [PubMed] [Google Scholar]
  19. Lefebvre A., Mauffret O., Lescot E., Hartmann B., Fermandjian S. Solution structure of the CpG containing d(CTTCGAAG)2 oligonucleotide: NMR data and energy calculations are compatible with a BI/BII equilibrium at CpG. Biochemistry. 1996 Sep 24;35(38):12560–12569. doi: 10.1021/bi9606298. [DOI] [PubMed] [Google Scholar]
  20. Leijon M., Zdunek J., Fritzsche H., Sklenar H., Gräslund A. NMR studies and restrained-molecular-dynamics calculations of a long A+T-rich stretch in DNA. Effects of phosphate charge and solvent approximations. Eur J Biochem. 1995 Dec 15;234(3):832–842. doi: 10.1111/j.1432-1033.1995.832_a.x. [DOI] [PubMed] [Google Scholar]
  21. Lipanov A., Kopka M. L., Kaczor-Grzeskowiak M., Quintana J., Dickerson R. E. Structure of the B-DNA decamer C-C-A-A-C-I-T-T-G-G in two different space groups: conformational flexibility of B-DNA. Biochemistry. 1993 Feb 9;32(5):1373–1389. doi: 10.1021/bi00056a024. [DOI] [PubMed] [Google Scholar]
  22. Lipscomb L. A., Peek M. E., Morningstar M. L., Verghis S. M., Miller E. M., Rich A., Essigmann J. M., Williams L. D. X-ray structure of a DNA decamer containing 7,8-dihydro-8-oxoguanine. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):719–723. doi: 10.1073/pnas.92.3.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Liu H., Spielmann H. P., Ulyanov N. B., Wemmer D. E., James T. L. Interproton distance bounds from 2D NOE intensities: effect of experimental noise and peak integration errors. J Biomol NMR. 1995 Dec;6(4):390–402. doi: 10.1007/BF00197638. [DOI] [PubMed] [Google Scholar]
  24. Mauffret O., Hartmann B., Convert O., Lavery R., Fermandjian S. The fine structure of two DNA dodecamers containing the cAMP responsive element sequence and its inverse. Nuclear magnetic resonance and molecular simulation studies. J Mol Biol. 1992 Oct 5;227(3):852–875. doi: 10.1016/0022-2836(92)90227-b. [DOI] [PubMed] [Google Scholar]
  25. Metzler W. J., Wang C., Kitchen D. B., Levy R. M., Pardi A. Determining local conformational variations in DNA. Nuclear magnetic resonance structures of the DNA duplexes d(CGCCTAATCG) and d(CGTCACGCGC) generated using back-calculation of the nuclear Overhauser effect spectra, a distance geometry algorithm and constrained molecular dynamics. J Mol Biol. 1990 Aug 5;214(3):711–736. doi: 10.1016/0022-2836(90)90288-W. [DOI] [PubMed] [Google Scholar]
  26. Pearlman D. A., Kollman P. A. Are time-averaged restraints necessary for nuclear magnetic resonance refinement? A model study for DNA. J Mol Biol. 1991 Jul 20;220(2):457–479. doi: 10.1016/0022-2836(91)90024-z. [DOI] [PubMed] [Google Scholar]
  27. Poncin M., Hartmann B., Lavery R. Conformational sub-states in B-DNA. J Mol Biol. 1992 Aug 5;226(3):775–794. doi: 10.1016/0022-2836(92)90632-t. [DOI] [PubMed] [Google Scholar]
  28. Privé G. G., Heinemann U., Chandrasegaran S., Kan L. S., Kopka M. L., Dickerson R. E. Helix geometry, hydration, and G.A mismatch in a B-DNA decamer. Science. 1987 Oct 23;238(4826):498–504. doi: 10.1126/science.3310237. [DOI] [PubMed] [Google Scholar]
  29. Privé G. G., Yanagi K., Dickerson R. E. Structure of the B-DNA decamer C-C-A-A-C-G-T-T-G-G and comparison with isomorphous decamers C-C-A-A-G-A-T-T-G-G and C-C-A-G-G-C-C-T-G-G. J Mol Biol. 1991 Jan 5;217(1):177–199. doi: 10.1016/0022-2836(91)90619-h. [DOI] [PubMed] [Google Scholar]
  30. Quintana J. R., Grzeskowiak K., Yanagi K., Dickerson R. E. Structure of a B-DNA decamer with a central T-A step: C-G-A-T-T-A-A-T-C-G. J Mol Biol. 1992 May 20;225(2):379–395. doi: 10.1016/0022-2836(92)90928-d. [DOI] [PubMed] [Google Scholar]
  31. Sarai A., Jernigan R. L., Mazur J. Interdependence of conformational variables in double-helical DNA. Biophys J. 1996 Sep;71(3):1507–1518. doi: 10.1016/S0006-3495(96)79353-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schmitz U., James T. L. How to generate accurate solution structures of double-helical nucleic acid fragments using nuclear magnetic resonance and restrained molecular dynamics. Methods Enzymol. 1995;261:3–44. doi: 10.1016/s0076-6879(95)61003-0. [DOI] [PubMed] [Google Scholar]
  33. Schmitz U., Pearlman D. A., James T. L. Solution structure of [d(GTATATAC)]2 via restrained molecular dynamics simulations with nuclear magnetic resonance constraints derived from relaxation matrix analysis of two-dimensional nuclear Overhauser effect experiments. J Mol Biol. 1991 Sep 5;221(1):271–292. doi: 10.1016/0022-2836(91)80219-k. [DOI] [PubMed] [Google Scholar]
  34. Schmitz U., Sethson I., Egan W. M., James T. L. Solution structure of a DNA octamer containing the Pribnow box via restrained molecular dynamics simulation with distance and torsion angle constraints derived from two-dimensional nuclear magnetic resonance spectral fitting. J Mol Biol. 1992 Sep 20;227(2):510–531. doi: 10.1016/0022-2836(92)90904-x. [DOI] [PubMed] [Google Scholar]
  35. Sodano P., Hartmann B., Rose T., Wain-Hobson S., Delepierre M. Solution structure of a homopyrimidine: homopurine dodecamer encoded by the HIV-1 envelope gene: NMR and molecular simulation studies. Biochemistry. 1995 May 23;34(20):6900–6910. doi: 10.1021/bi00020a038. [DOI] [PubMed] [Google Scholar]
  36. Timsit Y., Moras D. Self-fitting and self-modifying properties of the B-DNA molecule. J Mol Biol. 1995 Sep 1;251(5):629–647. doi: 10.1006/jmbi.1995.0461. [DOI] [PubMed] [Google Scholar]
  37. Timsit Y., Vilbois E., Moras D. Base-pairing shift in the major groove of (CA)n tracts by B-DNA crystal structures. Nature. 1991 Nov 14;354(6349):167–170. doi: 10.1038/354167a0. [DOI] [PubMed] [Google Scholar]
  38. Ulyanov N. B., Gorin A. A., Zhurkin V. B., Chen B. C., Sarma M. H., Sarma R. H. Systematic study of nuclear Overhauser effects vis-à-vis local helical parameters, sugar puckers, and glycosidic torsions in B DNA: insensitivity of NOE to local transitions in B DNA oligonucleotides due to internal structural compensations. Biochemistry. 1992 Apr 28;31(16):3918–3930. doi: 10.1021/bi00131a005. [DOI] [PubMed] [Google Scholar]
  39. Ulyanov N. B., Schmitz U., Kumar A., James T. L. Probability assessment of conformational ensembles: sugar repuckering in a DNA duplex in solution. Biophys J. 1995 Jan;68(1):13–24. doi: 10.1016/S0006-3495(95)80181-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yuan H., Quintana J., Dickerson R. E. Alternative structures for alternating poly(dA-dT) tracts: the structure of the B-DNA decamer C-G-A-T-A-T-A-T-C-G. Biochemistry. 1992 Sep 1;31(34):8009–8021. [PubMed] [Google Scholar]
  41. el antri S., Bittoun P., Mauffret O., Monnot M., Convert O., Lescot E., Fermandjian S. Effect of distortions in the phosphate backbone conformation of six related octanucleotide duplexes on CD and 31P NMR spectra. Biochemistry. 1993 Jul 20;32(28):7079–7088. doi: 10.1021/bi00079a003. [DOI] [PubMed] [Google Scholar]

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