Dynamics of Nucleic Acids and Nucleic Acid:Protein Complexes

  • Lennart Nilsson
Part of the Springer Series in Synergetics book series (SSSYN, volume 65)


Molecular dynamics simulations can shed light on subnanosecond phenomena in nucleic acids interacting with proteins. Results from studies of Ribonuclease T1, the glucocortoid receptor DNA binding domain, and short model nucleotides are reported, and compared to experimental NMR and fluorescence data. Events occurring on different timescales will be discussed, together with an analysis of the the role of water, especially in the interface between protein and DNA.


Glucocorticoid Receptor Free Energy Perturbation Half Site EcoRI Endonuclease Generalize Order Parameter 
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  1. 1.
    A. Elofsson, L. Nilsson “Free Energy Perturbations in Ribonuclease T\ Sub- # strate Binding. A Study of the Influence of Simulation Length, Internal Degrees of Freedom and Structure in Free Energy Perturbations” Mol. Sim. 10, 255–276 (1993).CrossRefGoogle Scholar
  2. 2.
    B.R. Brooks, R.E. Bruccoleri, B.D. Olafson, D.J. States, S. Swaminathan, M. Karplus “CHARMM: A Program for Macromolecular Energy, Minimization, and Dynamics Calculations” J. Comp. Chem. 4, 187–217 (1983).CrossRefGoogle Scholar
  3. 3.
    L. Nilsson, M. Karplus “Empirical Energy Functions for Energy Minimizations I and Dynamics of Nucleic Acids” J. Comp. Chem. 7, 591–616 (1986).CrossRefGoogle Scholar
  4. 4.
    L. Verlet “Computer ‘Experiments’ on Classical Fluids. I. Thermodynamical H Properties of Lennard-Jones Molecules” Phys. Rev. 159, 98–103 (1967).ADSCrossRefGoogle Scholar
  5. 5.
    J.P. Ryckaert, G. Ciccotti, H.J.C. Berendsen “Numerical Integration of the 1 Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-alkanes” Journal of Computational Physics 23, 327–341 (1977).ADSCrossRefGoogle Scholar
  6. 6.
    W.L. Jorgensen, J. Chandrasekhar, J. Madura, R.W. Impey, M.L. Klein “Comparison of Simple Potential Functions for Simulating Liquid Water” J. Chem. Phys. 79, 926–935 (1983).ADSCrossRefGoogle Scholar
  7. 7.
    C.L. Brooks, A.T. Brünger, M. Karplus “Active Site Dynamics in Protein Molecules: A Stochastic Boundary Molecular Dynamics Approac” Biopolymers 24, 843–865 (1985).CrossRefGoogle Scholar
  8. 8.
    G. Lipari, A. Szabo “A Model-free Approach to the Interpretation of Nuclear Magnetic Resonance Relaxation in Macromolecules. I. Theory and Range of Validity” J. Am. Chem. Soc.104, 4546–4559 (1982).CrossRefGoogle Scholar
  9. 9.
    C.A. Frederick, J. Grable, M. Melia, C. Samudzi, L. Jen-Jacobson, B.C. Wang, P. Greene, H.W. Boyer, J.M. Rosenberg “Kinked DNA in Crystalline Complex with EcoRI Endonuclease” Nature 309, 327–331 (1984).ADSCrossRefGoogle Scholar
  10. 10.
    Y. Kim, J.C. Grable, R. Love, P.J. Greene, J.M. Rosenberg “Refinement of EcoRI Endonuclease Crystal Structure: A Revised Chain Tracing” Science 249, 1307–1309 (1990).ADSCrossRefGoogle Scholar
  11. 11.
    T. Nordlund, S. Andersson, L. Nilsson, R. Rigler, A. Gräslund, L.W. McLaughlin “Structure and Dynamics of a Fluorescent DNA Oligomer Containing the EcoRI Recognition Sequence: Fluorescence, Molecular Dynamics, and NMR I Studies” Biochemistry 28, 9095–9103 (1989).CrossRefGoogle Scholar
  12. 12.
    R. Rigler, F. Claesens. “Picosecond Time Domain Spectroscopy of Structure and Dynamics in Nucleic Acids”, in Structure and Dynamics of RNA, eds.P.H. van Knippenberg and C.W. Hilbers (Plenum Press, New York 1986) pp. 45–54Google Scholar
  13. 13.
    J. Norberg, L. Nilsson. “Stacking-unstacking of the Dinucleoside Monophos phate Guanylyl-3’-5’-Uridine Studied with Molecular Dynamics” Biophysical Journal in press, 1994Google Scholar
  14. 14.
    J. Norberg, L. Nilsson “High Pressure Molecular Dynamics of a Nucleic Acid Fragment”, Chem. Phys. Lett, in pressGoogle Scholar
  15. 15.
    A.D. MacKerell, R. Rigler, L. Nilsson, U. Hahn, W. Saenger “Protein Dynamics: A Time-Resolved Fluorescence, Energetic and Molecular Dynamics Study of Ribonuclease Tl” Biophys. Chem.26, 247–261 (1987).CrossRefGoogle Scholar
  16. 16.
    A.D. MacKerell, R. Rigler, L. Nilsson, U. Heinemann, W. Saenger “Molecular Dynamics of Ribonuclease Tl: Effect of Solvent on the Interaction with 2’GMP” Eur. Biophys. J. 16, 287–297 (1988).CrossRefGoogle Scholar
  17. 17.
    A.D. MacKerell, L. Nilsson, R. Rigler, U. Heinemann, W. Saenger “Molecular 1 Dynamics of Ribonuclease Tl: Comparison of the Free Enzyme and the 2’GMP-Enzyme Complex” Proteins 6, 20–31 (1989).CrossRefGoogle Scholar
  18. 18.
    A.D. MacKerell, L. Nilsson, R. Rigler, W. Saenger “Molecular Dynamics Simulations of Ribonuclease Tl: Analysis of the Effect of Solvent on the Structure, Fluctuations and Active Site of the Free Enzyme” Biochemistry 27, 4547–4556 (1988).CrossRefGoogle Scholar
  19. 19.
    T. Härd, J.-Ä. Gustafsson “Structure and Function of the DNA-Binding Domain of the Glucocorticoid Receptor and other Members of the Nuclear Receptor Supergene Family” Acc. Chem. Res. 26, 644–650 (1993).CrossRefGoogle Scholar
  20. 20.
    M. Beato Cell 56, 335–344 (1989).CrossRefGoogle Scholar
  21. 21.
    T. Härd, E. Kellenbach, R. Boelens, R. Kaptein, K. Dahlman, J. Carlstedt- Duke, L.P. Freedman, B.A. Maler, E. Hyde, J.-Ä. Gustafsson, K.R. Yamamoto “H NMR Studies of the Glucocorticoid Receptor DNA-binding Domain: Sequential Assignments and Identification of Secondary Structure Elements” Bio- J chemistry 29, 9015–9023 (1990).Google Scholar
  22. 22.
    S.Y. Tsai, J. Carlstedt-Duke, N.L. Weigel, K. Dahlman, J.-Ä. Gustafsson, M.-J. Tsai, B.W. O’Malley “Molecular Interactions of Steroid Hormone Receptor with its Enhancer Element: Evidence for Receptor Dimer Formation” Cell 55, 361–369 (1988).CrossRefGoogle Scholar
  23. 23.
    T. Härd, E. Kellenbach, R. Boelens, B.A. Maler, K. Dahlman, L.P. Freedman, J. Carlstedt-Duke, K.R. Yamamoto, J.-Ä. Gustafsson, R. Kaptein “Solution Structure of the Glucocorticoid Receptor DNA-binding Domain” Science 249, 157–160 (1990).ADSCrossRefGoogle Scholar
  24. 24.
    B.F. Luisi, W.X. Xu, Z. Otwinowski, L.P. Freedman, K.R. Yamamoto, P.B. Sigler “Crystallographic Analysis of the Interaction of the Glucocorticoid Receptor with DNA“ Nature 352, 497–505 (1991).ADSCrossRefGoogle Scholar
  25. 25.
    P.J. Kraulis “MOLSCRIPT: A Program to Produce both Detailed and Schematic Plots of Protein Structures” J. Appl. Cryst.24, 946–950 (1991).CrossRefGoogle Scholar
  26. 26.
    M.A.L. Eriksson, H. Berglund, T. Härd, L. Nilsson “A Comparison of 15N NMR Relaxation Measurements With a Molecular Dynamics Simulation: Backbone Dynamics of the Glucocorticoid Receptor DNA-Binding Domain” Proteins 17, 375–390 (1993).CrossRefGoogle Scholar
  27. 27.
    M. Eriksson, T. Härd, L. Nilsson “Molecular Dynamics Simulation of a DNA Binding Protein Free and in Complex With DNA” in Computational Approaches to Supramolecular Chemistry, ed.G. Wipff (Kluwer, 1994)Google Scholar
  28. 28.
    J. Zilliacus, A.P.H. Wright, U. Norinder, J.-Ä. Gustafsson, J. Carlstedt-Duke “Determinants for DNA-binding Site Recognition by the Glucocorticoid Receptor” J. Biol. Chem. 267, 24941–24947 (1992).Google Scholar

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© Springer-Verlag Berlin Heidelberg 1995

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  • Lennart Nilsson

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