Skip to main content
SpringerLink
Log in

A molecular dynamics simulation study of polyamine– and sodium–DNA. Interplay between polyamine binding and DNA structure

  • Article
  • Published:
European Biophysics Journal Aims and scope Submit manuscript

Abstract

Four different molecular dynamics (MD) simulations have been performed for infinitely long ordered DNA molecules with different counterions, namely the two natural polyamines spermidine(3+) (Spd3+) and putrescine(2+) (Put2+), the synthetic polyamine diaminopropane(2+)(DAP2+), and the simple monovalent cation Na+. All systems comprised a periodical hexagonal cell with three identical DNA decamers, 15 water molecules per nucleotide, and counterions balancing the DNA charge. The simulation setup mimics the DNA state in oriented DNA fibers, previously studied using NMR and other experimental methods. In this paper the interplay between polyamine binding and local DNA structure is analyzed by investigating how and if the minor groove width of DNA depends on the presence and dynamics of the counterions. The results of the MD simulations reveal principal differences in the polyamine–DNA interactions between the natural [spermine(4+), Spd3+, Put2+] and the synthetic (DAP2+) polyamines.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6a, b
Fig. 7

Similar content being viewed by others

Abbreviations

DAP:

diaminopropane

DDD:

Drew–Dickerson dodecamer

MD:

molecular dynamics

Put:

putrescine

RDF:

radial distribution function

Spd:

spermidine

Spm:

spermine

References

  • Allen MP, Tildesley DJ (1987) Computer simulations of liquids. Clarendon, Oxford

  • Bevan DR, Li L, Pedersen LG, Darden TA (2000) Molecular dynamics simulations of the d(CCAACGTTGG)2 decamer: influence of the crystal environment. Biophys J 78:668–682

    CAS  PubMed  Google Scholar 

  • Bonvin AMJJ (2000) Localisation and dynamics of sodium counterions around DNA in solution from molecular dynamics simulations. Eur Biophys J 29:57–60

    Article  CAS  PubMed  Google Scholar 

  • Chiu TK, Dickerson RE (2000) 1 Å crystal structures of B-DNA reveal sequence-specific binding and groove-specific bending of DNA by magnesium and calcium. J Mol Biol 301:915–945

    Article  CAS  PubMed  Google Scholar 

  • Chiu TK, Kaczor-Grzeskowiak M, Dickerson RE (1999) Absence of minor groove monovalent cations in the crosslinked dodecamer C-G-C-G-A-A-T-T-C-G-C-G. J Mol Biol 292:589–608

    Article  CAS  PubMed  Google Scholar 

  • Cohen SL (1998) A guide to the polyamines. Oxford University Press, New York

  • Drew HR, Dickerson RE (1981) Structure of a B-DNA dodecamer III. Geometry of hydration. J Mol Biol 151:535–556

    CAS  PubMed  Google Scholar 

  • Egli M (2002) DNA–cation interactions: quo vadis? Chem Biol 9:277–286

    Article  CAS  PubMed  Google Scholar 

  • Hamelberg D, McFail-Isom L, Williams LD, Wilson WD (2000) Flexible structure of DNA: ion dependence of minor-groove structure and dynamics. J Am Chem Soc 122:10513–10520

    Article  CAS  Google Scholar 

  • Hamelberg D, Williams LD, Wilson WD (2001) Influence of the dynamic positions of cations on the structure of the DNA minor groove: sequence-dependent effects. J Am Chem Soc 123:7745–7755

    Article  CAS  PubMed  Google Scholar 

  • Hamelberg D, Williams LD, Wilson WD (2002) Effect of a neutralized phosphate backbone on the minor groove of B-DNA: molecular dynamics simulation studies. Nucleic Acids Res 30:3515–3623

    Article  Google Scholar 

  • Ho SP, Mooers BHM (1997) Z-DNA crystallography. Biopolymers 44:65–90

    Article  CAS  Google Scholar 

  • Howerton SB, Sines CC, VanDerveer L, Williams LD (2001) Locating monovalent cations in the grooves of B-DNA. Biochemistry 40:10023–10031

    Article  CAS  PubMed  Google Scholar 

  • Hud NV, Schultze P, Sklenár V, Feigon J (1999) Binding sites and dynamics of ammonium ions in the minor groove of DNA duplexes in solution and the origin of DNA A-tract bending. J Mol Biol 286:651–660

    Article  CAS  PubMed  Google Scholar 

  • Igarashi K, Kashiwagi K (2000) Polyamines: mysterious modulators of cellular functions. Biochem Biophys Res Commun 271:559–564

    Article  CAS  PubMed  Google Scholar 

  • Korolev N, Lyubartsev AP, Nordenskiöld L, Laaksonen A (2001) Spermine: an “invisible” component in the crystals of B-DNA. A grand canonical Monte Carlo and molecular dynamics simulation study. J Mol Biol 308:907–917

    Article  CAS  PubMed  Google Scholar 

  • Korolev N, Lyubartsev AP, Laaksonen A, Nordenskiöld L (2002) On the competition between water, sodium ions, and spermine in binding to DNA. A molecular dynamics computer simulation study. Biophys J 82:2860–2875

    CAS  PubMed  Google Scholar 

  • Korolev N, Lyubartsev AP, Laaksonen A, Nordenskiöld L (2003) A molecular dynamics simulation study of oriented DNA with polyamine and sodium counterions: diffusion and averaged binding of water and cations. Nucleic Acids Res 30:5971–5981

    Article  Google Scholar 

  • Korolev N, Lyubartsev AP, Laaksonen A, Nordenskiöld L (2004) Molecular dynamics simulation study of oriented polyamine– and Na–DNA: sequence specific interactions and effects on DNA structure. Biopolymers 73:542–555

    Article  CAS  PubMed  Google Scholar 

  • Kosikov KM, Gorin AA, Lu X-J, Olson WK, Manning GS (2002) Bending of DNA by asymmetric charge neutralization: all-atom energy simulations. J Am Chem Soc 124:4838–4847

    Article  CAS  PubMed  Google Scholar 

  • Lindsay SM, Lee SA, Powel JW, Weidlich T, DeMarco C, Lewen GD, Tao NJ, Rupprecht A (1988) The origin of the A to B transition in DNA fibers and films. Biopolymers 27:1015–1043

    CAS  PubMed  Google Scholar 

  • Lohikoski RA, Timonen J, Lyubartsev AP, Laaksonen A (2003) Internal structure and dynamics of the decamer d(ATGCAGTCAG)2 in Li+-H2O solution. A molecular dynamics simulation study. Mol Simul 29:47–62

    Article  CAS  Google Scholar 

  • Luger K, Richmond TJ (1998) DNA binding within the nucleosome core. Curr Opin Struct Biol 8:33–40

    CAS  PubMed  Google Scholar 

  • Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389:251–260

    CAS  PubMed  Google Scholar 

  • Lyubartsev AP, Laaksonen A (1998) Molecular dynamics simulations of DNA in solution with different counter-ions. J Biomol Struct Dyn 16:579–592

    CAS  PubMed  Google Scholar 

  • Lyubartsev AP, Laaksonen A (2000) M.DynaMix - a scalable portable parallel MD simulation package for arbitrary molecular mixtures. Comput Phys Commun 128:565–589

    Article  CAS  Google Scholar 

  • MacKerell AD, Wiorkiewiczkuczera J, Karplus M (1995) An all-atom empirical energy function for the simulation of nucleic-acids. J Am Chem Soc 117:11946–11975

    CAS  Google Scholar 

  • Maher JL (1998) Mechanisms of DNA bending. Curr Opin Chem Biol 2:688–694

    CAS  PubMed  Google Scholar 

  • Manning GS, Ebralidze KK, Mirzabekov AD, Rich A (1989) An estimate of the extent of folding of nucleosomal DNA by laterally asymmetric neutralization of phosphate groups. J Biomol Struct Dyn 6:877–889

    CAS  PubMed  Google Scholar 

  • Martyna GJ, Tobias DJ, Klein ML (1994) Constant pressure molecular dynamics algorithms. J Chem Phys 101:4177–4189

    Article  CAS  Google Scholar 

  • McConnell KJ, Beveridge DL (2000) DNA structure: what’s in charge? J Mol Biol 304:803–820

    Article  CAS  PubMed  Google Scholar 

  • McFail-Isom L, Sines CC, Williams LD (1999) DNA structure: cations in charge? Curr Opin Struct Biol 9:298–304

    Article  CAS  PubMed  Google Scholar 

  • Shui X, Sines CC, McFail-Isom L, VanDerveer L, Williams LD (1998) Structure of the potassium form of CGCGAATTCGCG: DNA deformation by electrostatic collapse around inorganic cations. Biochemistry 37:16877–16887

    Article  CAS  PubMed  Google Scholar 

  • Sines CC, McFail-Isom L, Howerton SB, VanDerveer L, Williams LD (2000) Cations mediate B-DNA conformational heterogenity. J Am Chem Soc 122:11048–11056

    Article  CAS  Google Scholar 

  • Smith DE, Dang LX (1994) Computer-simulations of NaCl association in polarizable water. J Chem Phys 100:3757–3766

    CAS  Google Scholar 

  • Song Z, Antzutkin ON, Lee YK, Shekar SC, Rupprecht A, Levitt MH (1997) Conformational transitions of the phosphodiester backbone in native DNA: two-dimensional magic-angle spinning 31P-NMR of DNA fibers. Biophys J 73:1539–1552

    CAS  PubMed  Google Scholar 

  • Stofer E, Lavery R (1994) Measuring the geometry of DNA grooves. Biopolymers 34:337–346

    CAS  PubMed  Google Scholar 

  • Thomas T, Thomas TJ (2001) Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications. Cell Mol Life Sci 58:244–258

    PubMed  Google Scholar 

  • Timsit Y, Moras D (1992) Crystallization of DNA. Methods Enzymol 211:409–429

    CAS  PubMed  Google Scholar 

  • Toukan K, Rahman A (1985) Molecular-dynamics study of atomic motions in water. Phys Rev B 31:2643–2648

    Article  CAS  Google Scholar 

  • Tuckerman M, Berne B, Martyna GJ (1992) Reversible multiple time scale molecular-dynamics. J Chem Phys 97:1990–2001

    Article  CAS  Google Scholar 

  • van Dam L, Korolev N, Nordenskiöld L (2002) Polyamine mobility and effect on DNA structure in oriented DNA fibers. Nucleic Acids Res 30:419–428

    Article  PubMed  Google Scholar 

  • Williams LD, Maher JL (2000) Electrostatic mechanisms of DNA deformation. Annu Rev Biophys Biomol Struct 29:497–521

    Article  CAS  PubMed  Google Scholar 

  • York DM, Yang W, Lee H, Darden T, Pedersen LG (1995) Toward the accurate modeling of DNA: the importance of long-range electrostatics. J Am Chem Soc 117:5001–5002

    CAS  Google Scholar 

Download references

Acknowledgements

This work has been supported by the Swedish Science Research Council. N.K. acknowledges the support for a research fellowship from the School of Biological Sciences, NTU and from the Biomedical Research Council (BMRC), Singapore.

Author information

Authors and Affiliations

  1. School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551

    Nikolay Korolev & Lars Nordenskiöld

  2. Division of Physical Chemistry, Arrhenius Laboratory, Stockholm University, 106 91 , Stockholm, Sweden

    Alexander P. Lyubartsev & Aatto Laaksonen

Authors
  1. Nikolay Korolev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander P. Lyubartsev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aatto Laaksonen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lars Nordenskiöld
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lars Nordenskiöld.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Korolev, N., Lyubartsev, A.P., Laaksonen, A. et al. A molecular dynamics simulation study of polyamine– and sodium–DNA. Interplay between polyamine binding and DNA structure. Eur Biophys J 33, 671–682 (2004). https://doi.org/10.1007/s00249-004-0410-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00249-004-0410-7

Keywords

Search

Navigation