Skip to main content
SpringerLink
Log in

Modelling DNA stretching for physics and biology

  • Published:
Genetica Aims and scope Submit manuscript

Abstract

We have used internal coordinate molecular mechanics calculations to study how the DNA double helix deforms upon stretching. Results obtained for polymeric DNA under helical symmetry constraints suggest that two distinct forms, an unwound ribbon and a narrow fibre, can be formed as a function of which ends of the duplex are pulled. Similar results are also obtained with DNA oligomers. These experiments lead to force curves which exhibit a plateau as the conformational transition occurs. This behaviour is confirmed by applying an increasing force to DNA and observing a sudden length increase at a critical force value. It is finally shown some DNA binding proteins can also stretch DNA locally, to conformations related to those created by nanomanipulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bensimon D.: Force: A new structural control parameter? Curr. Biol. 4 (1996): 885–889.

    Google Scholar 

  2. Austin R.H., Brody J.P., Cox E.C., Duke T. and T. Volkmuth T.: Stretch genes, Physics Today 50 (1997): 32–38.

    Google Scholar 

  3. Cluzel P., Lebrun A., Heller C., Lavery R., Viovy J.L., Chatenay D. and Caron F.: DNA: An extensible molecule, Science 271 (1996): 792–794.

    PubMed  Google Scholar 

  4. Smith S.B., Cui Y. and Bustamante C.: Overstretching B-DNA: The elastic response of individual double-stranded and single-stranded DNA molecules, Science 271 (1996): 795–799.

    PubMed  Google Scholar 

  5. Strick T.R., Allemand J.F., Bensimon D., Bensimon A. and Croquette V.: The elasticity of a single supercoiled DNA molecule, Science 271 (1996): 1835–1837.

    PubMed  Google Scholar 

  6. Strick T.R., Allemand J.F., Bensimon D. and Croquette V.: Behaviour of supercoiled DNA, Biophys. J. 74 (1998): 2016–2028.

    PubMed  Google Scholar 

  7. Allemand J.F., Bensimon D., Lavery R. and Croquette V.: Stretched and overtwound DNA forms a Pauling-like structure with exposed bases, Proc. Natl. Acad. Sci. USA (1998) 95, 14152–14157.

    PubMed  Google Scholar 

  8. Essevaz-Roulet B., Bockelmann U. and Heslot F.: Mechanical separation of the complementary strands of DNA, Proc. Natl. Acad. Sci. USA 94 (1997): 11935–11940.

    PubMed  Google Scholar 

  9. Bockelmann U., Essevaz-Roulet B. and Heslot F.: Molecular stick-slip revealed by opening DNA with piconewton force, Phys. Rev. Lett. 79 (1997): 4489–4492.

    Google Scholar 

  10. Tskhovrebova L. Trinick J., Sleep J.A. and Simmons R.M.: Elasticity and unfolding of single molecules of the giant muscle protein titin, Nature 387 (1997): 308–312.

    PubMed  Google Scholar 

  11. Rief M., Gautel M., Osterhelt F., Fernandez J.O. and Gaub H.E.: Reversible unfoldng of individual titin immunoglobulin domains by AFM, Science 276 (1997): 1109–1112.

    PubMed  Google Scholar 

  12. Kellermayer M.S.Z., Smith S.B., Granzier H.L. and Bustamante C.: Folding-unfolding transitions in single titin molecules characterized with laser tweezers, Science 276 (1997): 1112–1116.

    PubMed  Google Scholar 

  13. Florin E.-L., Moy V.T. and Gaub H.E.: Adhesion forces between individual ligand-receptor pairs, Science 264 (1994): 415–417.

    PubMed  Google Scholar 

  14. Lee G.U., Kidwell D.A. and Colton R.C.: Sensing discrete strepavidin-biotin interactions, Langmuir 10 (1994): 354–357.

    Google Scholar 

  15. Yin H., Wang M.D., Svoboda K., Landick R., Block S.M. and Gelles J.: Transcription against an applied force, Science 270 (1995): 1653–1657.

    PubMed  Google Scholar 

  16. Rief M., Oesterhelt F., Heymann B. and Gaub H.E.: Single molecule force spectroscopy on polysaccharides by atomic force microscopy, Science 275 (1997): 1295–1297.

    PubMed  Google Scholar 

  17. Evans E. and Ritchie K.: Dynamic strength of molecular adhesion bonds, Biophys. J. 72 (1997): 1541–1555.

    PubMed  Google Scholar 

  18. Lee G.U., Chrisey L.A. and Colton R.A.: Direct measurements of the forces between complementary strands of DNA, Science 266 (1994): 771–776.

    PubMed  Google Scholar 

  19. Noy A., Vezenov D.V., Kayyem J.F., Meade T.J. and Lieber C.M.: Stretching and breaking duplex DNA by chemical force microscopy, Chem. Biol. 4 (1997): 519–527.

    PubMed  Google Scholar 

  20. Lebrun A. and Lavery R.: Modelling extreme stretching of DNA, Nucleic Acids Res. 24 (1996): 2260–2270.

    PubMed  Google Scholar 

  21. Lebrun A. and Lavery R.: Modeling the mechanics of a DNA oligomer, J. Biomol. Struct. Dyn. (1998) 16, 593–604.

    PubMed  Google Scholar 

  22. Lavery R., Zakrzewska K. and Sklenar H.: JUMNA: Junction Minimization of Nucleic Acids, Comp. Phys. Commun. 91 (1995): 135–158.

    Google Scholar 

  23. Lavery R.: Junctions and bends in nucleic acids: A new theoretical approach. In: Olson W.K., Sarma M.H., Sarma R.H. and Sundaralingam M. (eds), Structure and Expression Vol. 3 DNA bending and curvature, Adenine Press, 1988, pp. 191–211.

  24. Werner M.H., Gronenborn A.M. and Clore G.M.: Intercalation, DNA kinking and the control of transcription, Science 271 (1996): 778–784.

    PubMed  Google Scholar 

  25. Lavery R., Parker I. and Kendrick J.: A general approach to the optimization of the conformation of ring molecules with an application to valinomycin, J. Biomol. Struct. Dyn. 4 (1986): 443–462.

    PubMed  Google Scholar 

  26. Hingerty B., Richie R.H., Ferrel T.L. and Turner J.E.: Dielectric effects in biopolymers; The theory of ionic saturation revisited, Biopolymers 24 (1985): 427–439.

    Google Scholar 

  27. Ahora N. and Jayaram B.: Strength of hydrogen bonds in α helices, J. Comp. Chem. 18 (1997): 1245–1252.

    Google Scholar 

  28. Flatters D., Zakrzewska K. and Lavery R. Internal coordinate modeling of DNA: Force field comparisons, J. Comp. Chem. 18 (1997): 1043–1055.

    Google Scholar 

  29. Weiner S.J., Kollman P.A., Nguyen D.T. and Case D.T.: An all atom force field for simulation of proteins and nucleic acids, J. Comp. Chem. 7 (1986): 230–252.

    Google Scholar 

  30. Cornell W.D., Cieplak P., Bayly C.I., Gould I.R., Merz Jr. K.M., Ferguson D.M., Spellmeyer D.C., Fox T., Caldwell J.W. and Kollman P.A.: A second generation force field for the simulation of proteins, nucleic acids and organic molecules, J. Am. Chem. Soc. 117 (1995): 5179–5197.

    Google Scholar 

  31. Sanghani S.R., Zakrzewska K., Harvey S.C. and Lavery R.: Molecular modelling of (A4T4NN) and (T4A4NN): Sequence elements responsible for curvature, Nucleic Acids Res. 24 (1996): 1632–1637.

    PubMed  Google Scholar 

  32. Lavery R. and Sklenar H.: Defining the structure of irregular nucleic acids: Conventions and principles, J. Biomol. Struct. Dyn. 6 (1989): 655–667.

    PubMed  Google Scholar 

  33. Bensimon A., Simon A., Chiffaudel A., Croquette V., Heslot F. and Bensimon D.: Alignment and sensitive detection of DNA by a receding meniscus, Science 265 (1994): 2096–2098.

    PubMed  Google Scholar 

  34. Allemand J.F., Bensimon D., Jullien L., Bensimon A. and Croquette V.: pH-dependent specific binding and combing of DNA, Biophys J. 73 (1997): 2064–2070.

    PubMed  Google Scholar 

  35. Gilson M.K., Sharp K.A. and Honig B.: Calculating the electrostatic potential of molecules in solution: method and error assessment, J. Comp. Chem. 9 (1987): 327–335.

    Google Scholar 

  36. Kim Y., Gieger J.H., Hahn S. and Sigler P.B.: Crystal structure of a yeast TBP/TATA-box complex, Nature 365 (1993): 512–520.

    PubMed  Google Scholar 

  37. Kim J.L., Nikolov D.B. and Burley S.K.: Co-crystal structure of TBP recognizing the minor groove of a TATA element, Nature 365 (1993): 520–527.

    PubMed  Google Scholar 

  38. Juo Z.S., Chiu T.K., Leiberman P.M., Baikalov I., Berk A.J. and Dickerson R.E.: How proteins recognize the TATA-box, J. Mol. Biol. 261 (1996): 239–254.

    PubMed  Google Scholar 

  39. Schumacher M.A., Choi K.Y., Zalkin H. and Brennan R.G.: Crystal structure of Lac1 member, PurR, bound to DNA: Minor groove binding by α helices, Science 266 (1994): 763–770.

    PubMed  Google Scholar 

  40. Love J.J., Li X., Case D.A., Glese K., Grosschedi R. and Wright P.E.: Structural basis for DNA bending by the architectural transcription factor LEF-1, Nature 376 (1995): 791–795.

    PubMed  Google Scholar 

  41. Werner M.H., Huth J.R., Gronenborn A.M. and Clore G.M.: Molecular basis of human 46X,Y sex reversal revealed from the three-dimensional solution structure of the human SRY-DNA complex, Cell 81 (1995): 705–714.

    PubMed  Google Scholar 

  42. Guzikevich-Guerstein G. and Shakked Z.: A novel form of the DNA double helix imposed on the TATA-box by the TATA-box binding protein, Nature Struct. Biol. 3 (1996): 32–37.

    PubMed  Google Scholar 

  43. Lebrun A., Shakked Z. and Lavery R.: Local DNA stretching mimics the distortion caused by the TATA-box binding protein, Proc. Natl. Acad. Sci. USA 94 (1997): 2993–2998.

    PubMed  Google Scholar 

  44. Lebrun A. and Lavery R.: Modeling DNA deformations induced by minor groove binding proteins, Biopolymers 45 (1999): 341–353.

    Google Scholar 

  45. Flatters D., Young M.A., Beveridge D.L. and Lavery R.: Conformational properties of the TATA-box binding sequence of DNA, J. Biomol. Struct. Dyn. 14 (1997): 757–794.

    PubMed  Google Scholar 

  46. Pastor N., Pardo L. and Weinstein H.: Does TATA matter? A structural exploration of the selectivity determinants in its complexes with TATA box-binding protein, Biophys.J. 73 (1997): 640–652.

    PubMed  Google Scholar 

  47. de Souza O.N. and Ornstein R.L.: Inherent DNA duplex curvature determined from 1.5 ns molecular dynamics simulations for a series of TATA-promoter mutants and comparison with experimental physical and biological observations, J. Biomol. Struct. Dyn. 14 (1997): 776.

    Google Scholar 

  48. Flatters D. and Lavery R.: Sequence dependent dynamics of TATA-box binding sites, Biophys. J. 75 (1998): 372–381.

    PubMed  Google Scholar 

  49. Pastor N., Pardo L. and Weinstein H.: How the TATA box selects its protein partner. In: Leotis N.B. and SantaLucia J. (eds), Molecular Modeling of Nucleic Acids. ACS Symp. series 682, 1998, 329–345.

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Biochimie Théorique, Institut de Biologie Physico‐Chimique, 13, rue Pierre et Marie Curie, 75005, Paris, France

    Richard Lavery & Anne Lebrun

Authors
  1. Richard Lavery
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne Lebrun
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lavery, R., Lebrun, A. Modelling DNA stretching for physics and biology. Genetica 106, 75–84 (1999). https://doi.org/10.1023/A:1003776827836

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1003776827836

Search

Navigation