Wang, B.; Chalk, C.; Doty, D.; Soloveichik, D.

Synthetic molecular information processing is typically designed through programming kinetic pathways, so that molecules bind, unbind, or incur conformational changes in some desired order. In contrast, thermodynamic programming focuses solely on the desired end-state rather than the path, often allowing simpler reasoning and requiring fewer parameters. Thermodynamic programming also naturally avoids energetically-favored, yet undesired, \"error\" states that often frustrate kinetic approaches. Here we demonstrate a thermodynamics-first paradigm based on the Thermodynamic Binding Networks (TBN) model, where the minimum free-energy configuration maximizes the number of separate complexes. We construct signal propagation circuits including fan-in and fan-out, seeded-assembly systems that perform Boolean logic computation, and systems for synthesis of concatemers of size quadratic in that of the substrates (by computing their least common multiple). Our work may enable new ways to engineer complex molecular behaviors and help inform the understanding of the computational power of kinetics versus thermodynamics for molecular systems.