Efficient Parameter Estimation for Oscillatory Biochemical Reaction Networks via a Genetic Algorithm with Adaptive Simulation Termination

Parameter estimation for biochemical reaction networks is computationally demanding, especially for systems with oscillatory nonlinear dynamics, where standard iterative optimization strategies, including genetic algorithms, often struggle with prohibitive computational costs. We introduce an efficient parameter estimation framework that combines a real-coded genetic algorithm with a novel adaptive simulation termination strategy. This strategy defines a time-dependent termination boundary based on population quantiles, which is permissive during early transients and becomes progressively stricter as simulations advance, explicitly accounting for the temporal structure of oscillatory behavior. Crucially, this mechanism facilitates the efficient identification and early simulation termination of poor parameter candidates, thus avoiding the computational expense of full-horizon simulations. The framework further integrates global exploration with the modified Powell method for rapid local refinement. Numerical experiments on two benchmark oscillatory models—the Lotka–Volterra and Goodwin oscillators—demonstrate that the framework reduces computational cost by approximately 30–50% compared to a baseline GA without this strategy. For the parameter-sensitive Goodwin model, the framework efficiently identifies candidates evolving toward damped oscillations caused by subtle parameter variations. Sensitivity analysis also confirms robustness across diverse hyperparameter settings, indicating that adaptive simulation termination provides a practical acceleration mechanism for inverse problems in systems biology where iterative objective function evaluation dominates runtime.