ATP-independent entropy-driven dsRNA unwinding by DDX3X revealed by coarse-grained simulations and deep learning.

DDX3X enables ATP-independent dsRNA unwinding in a coarse-grained RNA model, where separation occurs via rare, obligatory strand-displacing intermediates.

• Why it matters: ATP-independent unwinding by some DEAD-box helicases challenges the classic ATP-motor view, leaving the physical mechanism unresolved.
• What they did: The study builds a minimal physics-based coarse-grained RNA model with weak, specific DDX3X–dsRNA interactions and uses deep learning-assisted analysis to rank entropic contributions.
• The result: Unwinding is stochastic and requires overcoming an energy barrier, with entropy gain driving remodeling; hydrogen bonding is the dominant entropic factor, followed by base stacking and then backbone conformation.

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