High chemical affinity increases the robustness of biochemical oscillations.

Biochemical oscillations are ubiquitous in nature and allow organisms to properly time their biological functions. In this paper, we consider minimal Markov state models of nonequilibrium biochemical networks that support oscillations. We obtain analytical expressions for the coherence and period of oscillations in these networks. These quantities are expected to depend on all details of the transition rates in the Markov state model. However, our analytical calculations reveal that driving the system out of equilibrium makes many of these details-specifically, the location and arrangement of the transition rates-irrelevant to the coherence and period of oscillations. This theoretical prediction is confirmed by excellent agreement with numerical results. As a consequence, the coherence and period of oscillations can be robustly maintained in the presence of fluctuations in the irrelevant variables. While recent work has established that increasing energy consumption improves the coherence of oscillations, our findings suggest that it plays the additional role of making the coherence and the average period of oscillations robust to fluctuations in rates that can result from the noisy environment of the cell.