Atomistic simulations of nucleosomes

Nearly a dozen all-atom molecular dynamics (MD) simulations of the nucleosome have been performed. Collectively, these simulations provide insights into the structure and dynamics of the biomolecular complex that serves as the fundamental folding unit of chromatin. Nucleosomes contain 146 base pairs of DNA wrapped in a left-handed superhelix around a core of eight histones. This review provides a survey of what has been learned about DNA, histones, and solvent interactions based on all-atom MD studies of the nucleosome. The longest simulations to date are on the order of 100 nanoseconds. On this time scale, nucleosomes are quite stable. DNA kinks, the histone tails, solvent, and ions are highly dynamic and can be readily investigated using equilibrium dynamics methods. Steered MD is required to observe large-scale structural changes. The need for explicit solvent techniques is underscored by the inability of continuum solvent methods to properly describe the ion-nucleosome radial distribution functions. The atomistic techniques reviewed here are deemed necessary for exploration of the near infinite variations in atomic composition that exists even in the canonical nucleosome octamer. Continued development of these nascent simulation efforts will enable experimentalists to utilize rational design strategies in their efforts to investigate nucleosomes and chromatin. © 2013 John Wiley & Sons, Ltd.