Near-atomistic simulations reveal the molecular principles that control chromatin structure and phase separation
Abstract
Understanding how chromatin’s physicochemical properties shape its emergent organization is central to deciphering genome function. To address this, we present OpenCGChromatin, a high-performance coarse-grained model that achieves near-atomistic simulations of chromatin systems an order of magnitude larger than previously possible, spanning biomolecular condensates and fibers tens of kilobases in length. OpenCGChromatin simulations independently predict, from physicochemical principles, the linker-DNA-dependent chromatin structures observed by cryo-ET and the relative thermodynamic stability of condensates inferred from biochemical assays. Crucially, OpenCGChromatin resolves histone-tail dynamics and interaction networks that remain inaccessible experimentally, explaining how linker-DNA length controls histone tail accessibility and the resulting multiscale structure of chromatin condensates. Extending simulations to 108-nucleosome fibers shows that acetylation disrupts chromatin compaction in a pattern-specific manner by weakening key tail-mediated interactions, with H4K16 and H3K9 emerging as the most energetically disruptive modifications. These results position OpenCGChromatin as a powerful framework for linking molecular detail to emergent chromatin organization.
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BibTeX
@article{russell2026nearatomistic,
title = {{Near-atomistic simulations reveal the molecular principles that control chromatin structure and phase separation}},
author = {Kieran Russell and Yifang Chen and Jorge R. Espinosa and David Farré-Gil and Huabin Zhou and M. Julia Maristany and Jose Ignacio Perez-Lopez and Jan Huertas and Modesto Orozco and Michael K. Rosen and Rosana Collepardo-Guevara},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78050-6},
url = {https://www.nature.com/articles/s41467-026-78050-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Near-atomistic simulations reveal the molecular principles that control chromatin structure and phase separation
AU - Kieran Russell
AU - Yifang Chen
AU - Jorge R. Espinosa
AU - David Farré-Gil
AU - Huabin Zhou
AU - M. Julia Maristany
AU - Jose Ignacio Perez-Lopez
AU - Jan Huertas
AU - Modesto Orozco
AU - Michael K. Rosen
AU - Rosana Collepardo-Guevara
PY - 2026
DA - 2026/10/03
JO - Nature Communications
DO - 10.1038/s41467-026-78050-6
UR - https://www.nature.com/articles/s41467-026-78050-6
AB - Understanding how chromatin’s physicochemical properties shape its emergent organization is central to deciphering genome function. To address this, we present OpenCGChromatin, a high-performance coarse-grained model that achieves near-atomistic simulations of chromatin systems an order of magnitude larger than previously possible, spanning biomolecular condensates and fibers tens of kilobases in length. OpenCGChromatin simulations independently predict, from physicochemical principles, the linker-DNA-dependent chromatin structures observed by cryo-ET and the relative thermodynamic stability of condensates inferred from biochemical assays. Crucially, OpenCGChromatin resolves histone-tail dynamics and interaction networks that remain inaccessible experimentally, explaining how linker-DNA length controls histone tail accessibility and the resulting multiscale structure of chromatin condensates. Extending simulations to 108-nucleosome fibers shows that acetylation disrupts chromatin compaction in a pattern-specific manner by weakening key tail-mediated interactions, with H4K16 and H3K9 emerging as the most energetically disruptive modifications. These results position OpenCGChromatin as a powerful framework for linking molecular detail to emergent chromatin organization.
SN - 2041-1723
ER -