Molecular computation at equilibrium via programmable entropy.

Synthetic molecular information processing is typically designed through programming kinetic pathways, so that molecules bind, unbind, or incur conformational changes in some desired order. We demonstrate an alternative paradigm in dynamic DNA nanotechnology that programs the thermodynamic equilibrium state directly, with computation emerging from entropic driving forces. Like declarative programming in computer science, this approach emphasizes desired outcomes rather than specific steps, simplifying molecular programming and avoiding errors caused when thermodynamic forces work against programmed kinetics. We show broad applicability through three distinct applications: reversible signal propagation with fan-in and fan-out, algorithmic self-assembly performing Boolean logic, and synthesis of molecular chains (concatemers) of programmable length, illustrating how thermodynamic computation can enable practical molecular engineering tasks. Our work may enable previously unexplored ways to engineer complex molecular behaviors and help inform the understanding of the computational power of thermodynamics versus kinetics for molecular systems.