Thermoelastic mapping of DNA under coupled salt-temperature control with oxDNA2 coarse-grained simulations

Understanding how temperature and ionic strength jointly regulate DNA elasticity remains a central challenge in molecular biophysics, particularly in regimes where thermal fluctuations compete with electrostatic stabilization. Here, we employ the oxDNA2 coarse-grained framework to construct a systematic 3 × 9 salt–temperature map spanning 300–373 K and 0.5–1.5 M monovalent salt, enabling direct evaluation of dsDNA thermoelasticity under strong screening conditions. Across all ionic environments, the duplex softens progressively with temperature, although the extent of softening depends strongly on salt concentration. The bending persistence length decreases from ∼43 to 32 nm at 0.5 M, but only from ∼46 to 39 nm at 1.5 M, indicating that high salt suppresses thermal sensitivity by nearly 50%. Comparable trends are observed for the torsional persistence length, stretch modulus, and twist–stretch coupling. Despite this pronounced mechanical softening, hydrogen-bond occupancy remains above ∼ 90% throughout most of the explored range, demonstrating that elasticity deteriorates well before global duplex destabilization. Mechanistically, the simulations reveal that progressive weakening of base-stacking energetics, rather than hydrogen-bond disruption, is the dominant microscopic driver of thermoelastic softening. By introducing the dimensionless stacking parameter, χ = - 〈 E stack 〉 / k B T , we show that multiple elastic observables collapse onto near-universal scaling curves across the entire salt–temperature space. The resulting framework provides a unified statistical-mechanical description linking microscopic stacking thermodynamics to macroscopic DNA elasticity across coarse-grained, atomistic, and experimental regimes