title: The role of histone tails in the nucleosome: a computational study.
abstract: Histone tails play an important role in gene transcription and expression. We present here a systematic computational study of the role of histone tails in the nucleosome, using replica exchange molecular dynamics simulations with an implicit solvent model and different well-established force fields. We performed simulations for all four histone tails, H4, H3, H2A, and H2B, isolated and with inclusion of the nucleosome. The results confirm predictions of previous theoretical studies for the secondary structure of the isolated tails but show a strong dependence on the force field used. In the presence of the entire nucleosome for all force fields, the secondary structure of the histone tails is destabilized. Specific contacts are found between charged lysine and arginine residues and DNA phosphate groups and other binding sites in the minor and major DNA grooves. Using cluster analysis, we found a single dominant configuration of binding to DNA for the H4 and H2A histone tails, whereas H3 and H2B show multiple binding configurations with an equal probability. The leading stabilizing contribution for those binding configurations is the attractive interaction between the positively charged lysine and arginine residues and the negatively charged phosphate groups, and thus the resulting charge neutralization. Finally, we present results of molecular dynamics simulations in explicit solvent to confirm our conclusions. Results from both implicit and explicit solvent models show that large portions of the histone tails are not bound to DNA, supporting the complex role of these tails in gene transcription and expression and making them possible candidates for binding sites of transcription factors, enzymes, and other proteins.
authors.affiliation: Division of Biophysics of Macromolecules, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Erler
authors.affiliation: Division of Biophysics of Macromolecules, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Ruihan
authors.initials: R
authors.lastname: Zhang
authors.affiliation: UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
authors.forename: Loukas
authors.initials: L
authors.lastname: Petridis
authors.affiliation: UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Smith
authors.affiliation: Division of Biophysics of Macromolecules, German Cancer Research Center, Heidelberg, Germany. Electronic address: joerg.langowski@dkfz-heidelberg.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Langowski
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D006657:Histones; D009707:Nucleosomes; D004247:DNA