Computing and Bounding Equilibrium Concentrations in Athermic Chemical Systems

Abstract

Computing equilibrium concentrations of molecular complexes is generally analytically intractable and requires numerical approaches. In this work we focus on the polymer-monomer level, where indivisible molecules (monomers) combine to form complexes (polymers). Rather than employing free-energy parameters for each polymer, we focus on the athermic setting where all interactions preserve enthalpy. This setting aligns with the strongly bonded (domain-based) regime in DNA nanotechnology when strands can bind in different ways, but always with maximum overall bonding -- and is consistent with the saturated configurations in the Thermodynamic Binding Networks (TBNs) model. Within this context, we develop an iterative algorithm for assigning polymer concentrations to satisfy detailed-balance, where on-target (desired) polymers are in high concentrations and off-target (undesired) polymers are in low. Even if not directly executed, our algorithm provides effective insights into upper bounds on concentration of off-target polymers, connecting combinatorial arguments about discrete configurations such as those in the TBN model to real-valued concentrations. We conclude with an application of our method to decreasing leak in DNA logic and signal propagation. Our results offer a new framework for design and verification of equilibrium concentrations when configurations are distinguished by entropic forces.