BPS2026 – Probing open-state conformational dynamics in archaeal and telomeric nucleosomes using all-atom and coarse-grained molecular dynamics simulations

Across life, chromatin must strike a balance between stability and accessibility. Histone-based architectures achieve this through a mix of thermodynamic stability and dynamic flexibility; however, organisms use these principles in different ways. Archaeal histone filaments and human telomeric nucleosomes exemplify this, adopting stacked, linker-free architectures capable of sampling an open-lid conformation, with archaeal arrays additionally exhibiting slinky-like gyre fluctuations that modulate DNA accessibility. While these features are known, the mechanisms governing transitions between compact and accessible states remain unclear. Here, we sought to define how stacked nucleosome systems undergo open-state transitions and whether these reflect conserved or divergent evolutionary strategies. Using all-atom and coarse-grained simulations across microsecond-millisecond timescales, we constructed extended arrays under varying ionic conditions to probe stacking dynamics, gyre separations, and histone contact networks. Our results show that telomeric arrays exhibited bistable switching between stacked and unstacked states, stabilized by octamer interfaces, histone tails, and hinge contacts. In contrast, archaeal arrays remained compact, with accessibility emerging from continuous gyre fluctuations. These findings identify the open-lid conformation as a conserved feature of stacked nucleosomes while revealing that archaeal and telomeric systems have evolved distinct dynamic mechanisms to balance chromatin stability and accessibility.