Insights from All-Atom Molecular Dynamics Simulations of 40 Nucleosome Chromatin Fiber

Abstract

Gene expression is regulated, in part, by the organization of chromatin fiber, which is the next hierarchical level of chromatin compaction beyond the nucleosome. Due to the large size of the fiber - millions of atoms - computational studies investigating its organization have typically used coarse-grain simulations. Such simulations use customized, relatively unproven, force fields, and fail to elicit the finer details of the atom level structure. We use multiscale all-atom simulations of 40 nucleosome (over 1 million atom) chromatin fiber to study its structure and response to modifications such as post-translational modifications implicated in chromatin remodeling. The multiscale method used, Hierarchical Charge Partitioning (HCP), exploits the natural organization of biomolecules (atoms, groups, chains, and complexes), to speedup implicit solvent simulations of the fiber by over 2 orders of magnitude. The method uses the proven Amber force field to compute interactions between nearby atoms, while approximating interactions with distant components by a smaller number of charges that optimally reproduce the low order multipole moments of these components. We use the novel technique to gain insight into the organization of the more flexible regions of the fiber, such as linker DNA and histone tails.