IEEE Trans Biomed Circuits Syst. 2007 Jun;1(2):91-104. doi: 10.1109/TBCAS.2007.907060.
Based on the steady-state analyses of the synergism and saturation system (S-system) model, a robust control method is proposed for biochemical networks via feedback and feedforward biochemical circuits. Two robust biochemical circuit design schemes are developed. One scheme is to improve the system's structural stability so as to tolerate larger kinetic parameter variations, whereas the other is to compensate for the kinetic parameter variations to eliminate their effects. In addition, a multi-objective biochemical circuit design scheme is introduced for both the robust design against kinetic parameter variations and a desired sensitivity design to eliminate the effect of external disturbance simultaneously. The proposed robust circuit design schemes will provide a systematic method with potential applications in synthetic circuit design for biotechnological purpose and drug design purpose. Recent advances in both metabolic and genetic engineering have made the robust biochemical circuit control approach feasible through the design and implementation of synthetic biological networks amenable to mathematical modeling and quantitative analysis. Finally, several examples including the robust circuit design of the tricarboxylic acid cycle are used in silico to illustrate the design procedure and to confirm the performance of the proposed design method.
基于协同作用和饱和系统（S 系统）模型的稳态分析，通过反馈和前馈生化电路为生化网络提出了一种鲁棒控制方法。开发了两种鲁棒生化电路设计方案。一种方案是提高系统的结构稳定性，从而能够承受更大的动力学参数变化，而另一种方案是补偿动力学参数变化以消除其影响。此外，还介绍了一种多目标生化电路设计方案，用于同时抵抗动力学参数变化的鲁棒设计和消除外部干扰影响的期望灵敏度设计。所提出的鲁棒电路设计方案将为合成电路设计提供一种系统的方法，具有生物技术和药物设计目的的潜在应用。代谢和遗传工程的最新进展通过设计和实施可进行数学建模和定量分析的合成生物网络，使鲁棒生化电路控制方法成为可能。最后，使用几个示例（包括三羧酸循环的鲁棒电路设计）进行了计算机模拟，以说明设计过程并确认所提出设计方法的性能。
