Stochastic modeling of biochemical systems with multistep reactions using state-dependent time delay.

To deal with the growing scale of molecular systems, sophisticated modelling techniques have been designed in recent years to reduce the complexity of mathematical models. Among them, a widely used approach is delayed reaction for simplifying multistep reactions. However, recent research results suggest that a delayed reaction with constant time delay is unable to describe multistep reactions accurately. To address this issue, we propose a novel approach using state-dependent time delay to approximate multistep reactions. We first use stochastic simulations to calculate time delay arising from multistep reactions exactly. Then we design algorithms to calculate time delay based on system dynamics precisely. To demonstrate the power of proposed method, two processes of mRNA degradation are used to investigate the function of time delay in determining system dynamics. In addition, a multistep pathway of metabolic synthesis is used to explore the potential of the proposed method to simplify multistep reactions with nonlinear reaction rates. Simulation results suggest that the state-dependent time delay is a promising and accurate approach to reduce model complexity and decrease the number of unknown parameters in the models.