An advanced coarse-grained nucleosome core particle model for computer simulations of nucleosome-nucleosome interactions under varying ionic conditions

PLoS One. 2013;8(2):e54228. doi: 10.1371/journal.pone.0054228. Epub 2013 Feb 13.

Abstract

In the eukaryotic cell nucleus, DNA exists as chromatin, a compact but dynamic complex with histone proteins. The first level of DNA organization is the linear array of nucleosome core particles (NCPs). The NCP is a well-defined complex of 147 bp DNA with an octamer of histones. Interactions between NCPs are of paramount importance for higher levels of chromatin compaction. The polyelectrolyte nature of the NCP implies that nucleosome-nucleosome interactions must exhibit a great influence from both the ionic environment as well as the positively charged and highly flexible N-terminal histone tails, protruding out from the NCP. The large size of the system precludes a modelling analysis of chromatin at an all-atom level and calls for coarse-grained approximations. Here, a model of the NCP that include the globular histone core and the flexible histone tails described by one particle per each amino acid and taking into account their net charge is proposed. DNA wrapped around the histone core was approximated at the level of two base pairs represented by one bead (bases and sugar) plus four beads of charged phosphate groups. Computer simulations, using a Langevin thermostat, in a dielectric continuum with explicit monovalent (K(+)), divalent (Mg(2+)) or trivalent (Co(NH(3))(6) (3+)) cations were performed for systems with one or ten NCPs. Increase of the counterion charge results in a switch from repulsive NCP-NCP interaction in the presence of K(+), to partial aggregation with Mg(2+) and to strong mutual attraction of all 10 NCPs in the presence of CoHex(3+). The new model reproduced experimental results and the structure of the NCP-NCP contacts is in agreement with available data. Cation screening, ion-ion correlations and tail bridging contribute to the NCP-NCP attraction and the new NCP model accounts for these interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Nucleus / metabolism*
  • Computer Simulation
  • Ions
  • Models, Molecular*
  • Nucleic Acid Conformation
  • Nucleosomes / metabolism*

Substances

  • Ions
  • Nucleosomes

Grants and funding

This work has been supported by the Singapore Agency for Science Technology and Research (A*STAR) through the Biomedical Research Council (LN) (http://www.a-star.edu.sg) grant no. 10/1/22/19/666, by the Singapore Ministry of Education Academic Research Fund (AcRF) through a Tier 1, grant no. M52080112 RG46/10 (LN), and by the Swedish Research Council (http://www.vr.se) grant. no 621-2010-5005 (to APL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.