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Issue 20, 2015
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The histone H3 N-terminal tail: a computational analysis of the free energy landscape and kinetics

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Abstract

Histone tails are the short peptide protrusions outside of the nucleosome core particle and they play a critical role in regulating chromatin dynamics and gene activity. A histone H3 N-terminal tail, like other histone tails, can be covalently modified on different residues to activate or repress gene expression. Previous studies have indicated that, despite its intrinsically disordered nature, the histone H3 N-terminal tail has regions of notable secondary structural propensities. To further understand the structure–dynamics–function relationship in this system, we have carried out 75.6 μs long implicit solvent simulations and 29.3 μs long explicit solvent simulations. The extensive samplings allow us to better characterize not only the underlying free energy landscape but also kinetic properties through Markov state models (MSM). Dihedral principal component analysis (dPCA) and locally scaled diffusion map (LSDMap) analysis yield consistent results that indicate an overall flat free energy surface with several shallow basins that correspond to conformations with a high α-helical propensity in two regions of the peptide. Kinetic information extracted from Markov state models reveals rapid transitions between different metastable states with mean first passage times spanning from several hundreds of nanoseconds to hundreds of microseconds. These findings shed light on how the dynamical nature of the histone H3 N-terminal tail is related to its function. The complementary nature of dPCA, LSDMap and MSM for the analysis of biomolecules is also discussed.

Graphical abstract: The histone H3 N-terminal tail: a computational analysis of the free energy landscape and kinetics

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Supplementary files

Article information


Submitted
30 Mar 2015
Accepted
23 Apr 2015
First published
24 Apr 2015

This article is Open Access

Phys. Chem. Chem. Phys., 2015,17, 13689-13698
Article type
Paper
Author version available

The histone H3 N-terminal tail: a computational analysis of the free energy landscape and kinetics

Y. Zheng and Q. Cui, Phys. Chem. Chem. Phys., 2015, 17, 13689
DOI: 10.1039/C5CP01858G

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