Investigation of histone-DNA binding energy as a function of DNA unwrapping from nucleosome using molecular modeling

  • A. K. Gribkova
  • G. A. Armeev
  • A. K. ShaytanEmail author
Molecular Biology


The present study contributes to the understanding of DNA compaction in the cell nucleus at the nucleosomal level. The interaction between DNA and histones affects key processes of cell life, including replication and transcription. This interaction can be described in terms of a free energy profile. In this paper, we calculated the free energy profile during DNA unwrapping from the histone octamer. The calculations were carried out using the MM/PBSA method. The calculated profiles are in good agreement with experimental data published earlier. The obtained results indicate the applicability of the technique for studying the effect of posttranslational modifications of histones and histone variants on nucleosome energy, which is important for understanding the mechanisms of transcriptional regulation in chromatin.


nucleosome chromatin molecular dynamics MM/PBSA free energy calculations DNA histones 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Shaytan, A.K., Landsman, D., and Panchenko, A.R., Nucleosome adaptability conferred by sequence and structural variations in histone H2A-H2B dimers, Curr. Opin. Struct. Biol., 2015, vol. 32, pp. 48–57.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Brower-Toland, B.D., Smith, C.L., Yeh, R.C., Lis, J.T., Peterson, C.L., and Wang, M.D., Mechanical disruption of individual nucleosomes reveals a reversible multistage release of DNA, Proc. Natl. Acad. Sci. U.S.A., 2002, vol. 99, no. 4, pp. 1960–1965.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Thåström, A., Gottesfeld, J.M., Luger, K., and Widom, J., Histone-DNA binding free energy cannot be measured in dilution-driven dissociation experiments, Biochemistry, 2004, vol. 43, no. 3, pp. 736–741.CrossRefPubMedGoogle Scholar
  4. 4.
    Mihardja, S., Spakowitz, A.J., Zhang, Y., and Bustamante, C., Effect of force on mononucleosomal dynamics, Proc. Natl. Acad. Sci. U.S.A., 2006, vol. 103, no. 43, pp. 15871–15876.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Ettig, R., Kepper, N., Stehr, R., Wedemann, G., and Rippe, K., Dissecting DNA-histone interactions in the nucleosome by molecular dynamics simulations of DNA unwrapping, Biophys. J., 2011, vol. 101, no. 8, pp. 1999–2008.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Zhang, B., Zheng, W., Papoian, G.A., and Wolynes, P.G., Exploring the free energy landscape of nucleosomes, J. Am. Chem. Soc., 2016, vol. 138, no. 26, pp. 8126–8133.CrossRefPubMedGoogle Scholar
  7. 7.
    Kollman, P.A., et al., Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models, Acc. Chem. Res., 2000, vol. 33, no. 12, pp. 889–897.CrossRefPubMedGoogle Scholar
  8. 8.
    Davey, C.A., Sargent, D.F., Luger, K., Maeder, A.W., and Richmond, T.J., Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 Å resolution, J. Mol. Biol., 2002, vol. 319, no. 5, pp. 1097–1113.CrossRefPubMedGoogle Scholar
  9. 9.
    Banks, D.D. and Gloss, L.M., Equilibrium folding of the core histones: The H3-H4 tetramer is less stable than the H2A-H2B dimer, Biochemistry, 2003, vol. 42, no. 22, pp. 6827–6839.CrossRefPubMedGoogle Scholar
  10. 10.
    Armeev, G.A., Shaitan, K.V., and Shaytan, A.K., Nucleosome structure relaxation during DNA unwrapping: Molecular dynamics simulation study, Moscow Univ. Biol. Sci. Bull., 2016, vol. 71, no. 3, pp. 141–144.CrossRefGoogle Scholar
  11. 11.
    Guy, A.T., Piggot, T.J., and Khalid, S., Singlestranded DNA within nanopores: Conformational dynamics and implications for sequencing; A molecular dynamics simulation study, Biophys. J., 2012, vol. 103, no. 5, pp. 1028–1036.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Pronk, S., Páll, S., Schulz, R., Larsson, P., Bjelkmar, P., Apostolov, R., Shirts, M.R., Smith, J.C., Kasson, P.M., van der Spoel, D., Hess, B., and Lindahl, E., GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit, Bioinformatics, 2013, vol. 29, no. 7, pp. 845–854.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Humphrey, W., Dalke, A., and Schulten, K., VMD: Visual molecular dynamics, J. Mol. Graphics, 1996, vol. 14, no. 1, pp. 33–38.CrossRefGoogle Scholar
  14. 14.
    Forties, R.A., North, J.A., Javaid, S., Tabbaa, O.P., Fishel, R., Poirier, M.G., and Bundschuh, R., A quantitative model of nucleosome dynamics, Nucleic Acid Res., 2011, vol. 39, no. 19, pp. 8306–8313.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Allerton Press, Inc. 2017

Authors and Affiliations

  • A. K. Gribkova
    • 1
  • G. A. Armeev
    • 1
  • A. K. Shaytan
    • 1
    Email author
  1. 1.Department of BiologyMoscow State UniversityMoscowRussia

Personalised recommendations