Microscopic DNA fluctuations are in accord with macroscopic DNA stretching elasticity without strong dependence on force-field choice

  • John Marko
  • Michael Feig
  • B. Montgomery Pettitt
Part of the NATO Science Series book series (NAII, volume 116)


Multiscale modeling requires the use of information at small length and time scales to parameterize less detailed models at large scales/ We present analysis of molecular dynamics simulation of the solvated double-stranded DNA decamer d(C5T5) (A5G5) to parameterize an elastic rod model of DNA. We show that thermal fluctuation of rise along the helix implies stretching elasticity in accord with the macroscopic stretching elasticity observed in single- molecule stretching experiments. We find consistent results from three different force-fields (AMBER, CHARMM and CHARMM-27). Notably, while the base-pair rise averages about 3 Å, it fluctuates between 2 and 4 Å, i.e. by ±30%. The lifetime of these fluctuations is roughly one nanosecond. We discuss how these strong thermal deformations may play a role in the binding dynamics of proteins and drugs that deform double helix structure.


Multiscale Simulation Molecular Dynamics Field Theory 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Saenger, W. Principles of Nucleic Acid Structure, Springer Verlag: New York, 1984CrossRefGoogle Scholar
  2. [2]
    Drew, H.R.; Wing, R.M.; Takano, T.; Broka, C.; Tanaka, S.; Itakura, K.; Dickerson, R.E. Proc. Natl. Acad. Sci. USA 1981, 78, 2179CrossRefGoogle Scholar
  3. [3]
    Rhodes, G. Crystallography made crystal clear: A guide for users of macromolecular models, Academic Press: San Diego, 1993Google Scholar
  4. [4]
    Berman, H.M.; Olson, W.K.; Beveridge, D.L.; Westbrook, J.; Gelbin, A.; Demeny, T.; Hsieh, S.-H.; Srinivasan, A.R.; Schneider, B. Biophys. J. 1992, 63, 751CrossRefGoogle Scholar
  5. [5]
    Olson, W.K.; Zhurkin, V.B. Curr. Opin. Struct. Biol. 2000, 10, 286CrossRefGoogle Scholar
  6. [6]
    Levitt, M. Cold Spring Harb. Symp. Quant. Biol. 1983, 47, 251CrossRefGoogle Scholar
  7. [7]
    Keepers, J.W.; Kollman, P.A.; Weiner, P.K.; James, T.L. Proc. Natl. Acad. Sci. USA 1982, 79, 5537.CrossRefGoogle Scholar
  8. [8]
    Prabhakaran, M.; Harvey, S.C.; Mao, B.; MacCammon, J.A. J. Biomol. Struct. Dyn. 1983, 1, 357.CrossRefGoogle Scholar
  9. [9]
    Seibel, G.L.; Singh, U.C.; Kollman, P.A. Proc. Natl. Acad. Sci. USA 1985, 82, 6537CrossRefGoogle Scholar
  10. [10]
    Young, M.A.; Ravishanker, G.; Beveridge, D.L. Biophys. J 1997, 73, 2313Google Scholar
  11. [11]
    Sprous, D.; Young, M.A.; Beveridge, D.L. J. Mol. Biol. 1999, 285, 1623CrossRefGoogle Scholar
  12. [12]
    Masumoto, A.; Olson, W.K. Biophys. J. 2002, 83, 22CrossRefGoogle Scholar
  13. [13]
    Kosikov, K.M.; Gorin, A.A.; Zhurkin, V.B.; Olson, W.K. J. Mol. Biol. 1999, 289, 1301CrossRefGoogle Scholar
  14. [14]
    Schurr, J.M.; Fujimoto, B.S. Biopolymers 1999, 49, 355CrossRefGoogle Scholar
  15. [15]
    Lankas, F.; Sponer, J.; Hobza, P.; Langowski, J. J. Mol. Biol. 2000, 299, 695CrossRefGoogle Scholar
  16. [16]
    Hagerman, P.J.; Ann. Rev. Biophys. Chem. 1988, 17, 265CrossRefGoogle Scholar
  17. [17]
    Olson, W.K.; Marky, N.L.; Jernigan, R.L.; Zhurkin, V.B.; J. Mol. Biol. 1993, 232, 530CrossRefGoogle Scholar
  18. [18]
    Trifonov, E.N.; CRC Critical Reviews in Biochemistry CRC Press: Boca Raton, 1986; Vol. 19, pp 89–106Google Scholar
  19. [19]
    Calladine, C.R.; Drew, H.R.; McCall, M.J. J. Mol. Biol. 1988, 201, 127 Google Scholar
  20. [20]
    Landau, L.D.; Lifshitz, E.M. Theory of Elasticity, Pergamon Press: New York, 1986; Chs. I-IIGoogle Scholar
  21. [21]
    Cluzel, P.; Lebrun, A.; Heller, C.; Lavery, R.; Viovy, J.-L.; Chatenay, D. Caron, F. Science 1996, 271, 792CrossRefGoogle Scholar
  22. [22]
    Smith, S.B.; Cui, Y.; Bustamante, C. Science 1996, 271, 795CrossRefGoogle Scholar
  23. [23]
    Wang, M.D.; Yin, H.; Landick, R.; Gelles, J.; Block, S.M. Biophys. J. 1997, 72, 1335CrossRefGoogle Scholar
  24. [24]
    Chalikian, T.V.; Völker, J.; Plum, G.E.; Breslauer, K.J. Proc. Natl. Acad. Sci. USA 1999, 96, 7853CrossRefGoogle Scholar
  25. [25]
    Marko, J.F. Phys. Rev. E 1998, 57, 2134CrossRefGoogle Scholar
  26. [26]
    Feig, M.; Pettitt, B.M. Biophys. J. 1998, 75, 134CrossRefGoogle Scholar
  27. [27]
    Cornell, W.D.; Cieplak, P.; Bayly, C.I.; Gould, I.R.; Merz, K.M.; Ferguson, D.M.; Spellmeyer, D.C.; Fox, T.; Caldwell, J.W.; Kollman, P.A. J. Amer. Chem. Soc. 1995, 117, 5179CrossRefGoogle Scholar
  28. [28]
    MacKerell Jr., A.D.; Wiorkiewicz-Juczera, J.; Karplus, M. J. Amer. Chem. Soc. 1995, 117, 11946CrossRefGoogle Scholar
  29. [29]
    See http://yuri.harvard.eduGoogle Scholar
  30. [30]
    Dickerson, R.E. J. Biomol. Struct. Dyn. 1989, 6, 627CrossRefGoogle Scholar
  31. [31]
    Lavery, R.; Sklenar, H. J. Biomol. STruct. Dyn. 1989, 6, 655CrossRefGoogle Scholar
  32. [32]
    Stasiak, A.; di Capua, E.; Koller, Th. J. Mol. Biol. 1981, 151, 557CrossRefGoogle Scholar
  33. [33]
    Bruant, N.; Flatters, D.; Lavery, R.; Genest, D. Biophys. J. 1999, 77, 2366CrossRefGoogle Scholar
  34. [34]
    Doi, M.; Edwards, S.F.; Theory of Polymer Dynamics, Cambridge University Press, Cambridge: 1989; Sec. 3.5Google Scholar
  35. [35]
    Matsumoto, A.; Go, N. J. Chem. Phys. 1999, 110, 11070CrossRefGoogle Scholar
  36. [36]
    Bonnet, G.; Krichevsky, O.; Libchaber, A. Proc. Natl. Acad. Sci. USA 1999, 95, 8602CrossRefGoogle Scholar
  37. [37]
    Georghiou, S.; Bradrick, T.D.; Philippetis, A.; Beechem, J.M. Biophys. J. 1996, 70, 1909CrossRefGoogle Scholar
  38. [38]
    Brauns, E.B.; Madaras, M.L.; Coleman, R.S.; Murphy, C.J.; Berg, M.A. J. Am. Chem. Soc. 1999, 121, 11644CrossRefGoogle Scholar
  39. [39]
    Leger, J.F.; Robert, J.; Bourdieu, L.; Chatenay, D.; Marko, J.F. Proc. Natl. Acad. Sci. USA 1998, 95, 12295CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • John Marko
    • 1
  • Michael Feig
    • 2
  • B. Montgomery Pettitt
    • 3
  1. 1.Department of PhysicsThe University of Illinois at ChicagoChicagoUSA
  2. 2.Department of Molecular Biology TPC6The Scripps Research InstituteLa JollaUSA
  3. 3.Department of ChemistryThe University of HoustonHoustonUSA

Personalised recommendations