Optimal Control of Chemical Reaction Networks with Thermodynamic Cost

Abstract

Thermodynamic control seeks to realize desired functions at minimal thermodynamic cost, yet existing frameworks remain largely confined to slow driving regimes or state-to-state transport. Here we establish a thermodynamic optimal-control theory for Markov jump processes (MJPs) and chemical reaction networks (CRNs) that accommodates objectives over both states and reaction fluxes beyond slow-driving limit. By deriving the thermodynamic Hamilton--Jacobi--Bellman equation, we demonstrate that the optimal dynamics take the form of a perturbed generalized-gradient flow driven by the value function. A convex representation of the entropy-production rate via generalized means identifies its Legendre--Fenchel dual as the dissipation function. The resulting dynamics shares the thermodynamic structure of CRNs and admits an information-geometric characterization. We further derive a thermodynamic Pontryagin equation by recasting the control problem in terms of thermodynamic forces, providing a complementary description of optimal trajectories and clarifying connections to thermodynamic optimal transport. Our results establish a thermodynamic and geometric foundation for controlling MJPs and CRNs beyond mere transport, opening avenues for optimizing biological processes and finite-time thermodynamic operations in far-from-equilibrium regimes.