Exploring dissipative sources of non-Markovian biochemical reaction systems

Many biological processes including important intracellular processes are governed by biochemical reaction networks. Usually, these reaction systems operate far from thermodynamic equilibrium, implying free-energy dissipation. On the other hand, single reaction events happen often in a memory manner, leading to non-Markovian kinetics. A question then arises: how do we calculate free-energy dissipation (defined as the entropy production rate) in this physically real case? We derive an analytical formula for calculating the energy consumption of a general reaction system with molecular memory characterized by nonexponential waiting-time distributions. It shows that this dissipation is composed of two parts: one from broken detailed balance of an equivalent Markovian system with the same topology and substrates, and the other from the direction-time dependence of waiting-time distributions. But, if the system is in a detailed balance and the waiting-time distribution is direction-time independent, there is no energy dissipation even in the non-Markovian case. These general results provide insights into the physical mechanisms underlying nonequilibrium processes. A continuous-time random-walk model and a generalized model of stochastic gene expression are chosen to clearly show dissipative sources and the relationship between energy dissipation and molecular memory.

Automated summary

Biological processes are controlled by biochemical reaction networks operating far from thermodynamic equilibrium, dissipated free energy. Single reaction events occur in a memory manner, leading to non-Markovian kinetics. By calculating the energy consumption of a general reaction system with molecular memory, it is revealed that energy dissipation is influenced by broken detailed balance and direction-time dependence of waiting-time distributions.