Extended Data Fig. 3: Principles of reset success.

a, Desired and competing reactions during the reset of a catalytic circuit. b, NUPACK melting analysis of the desired (GY) and undesired (GF and YR) products. For analysis of the undesired products, the single strand G–Y was separated into a strand G (before the linker domain L) and a strand Y (after the linker domain L). Concentration of G–Y, G, and Y was set to 100 nM. Concentration of F and R was set to 200 nM. The difference in melting temperature between the desired and undesired products is roughly 4 °C. c, Simulations for exploring the impact of kinetics without changing the melting temperatures. Compared to the original rate constants (top plot), the forward and reverse rates for the desired hairpin closing reaction were slowed down simultaneously by a factor of 100 (middle plot) and 1000 (bottom plot). With a 100 times slowdown, the desired unimolecular reaction remains 3.9 times faster than the undesired bimolecular reactions, resulting in a small 6.2% decrease in the reset success rate of GY. With a 1000 times slowdown, the desired unimolecular reaction becomes 2.6 times slower than the undesired bimolecular reactions, resulting in a large 56.4% decrease in the reset success rate. d-f, Simulations for exploring the impact of cooling time (d), concentration (e), and linker size (f) on reset success. A 9.7% decrease in the reset success rate is observed when the cooling time is increased by 4 orders of magnitude from 1 to 10⁴ seconds. A much larger decrease in the reset success rate (84.6% or 97.1%, respectively) is observed when the concentration is increased to result in 4 orders of magnitude increase in the undesired bimolecular rates or when the linker size is increased to result in similar orders of magnitude decrease in the desired unimolecular reaction rate.