Renewed interest in dynamic simulation models of biomolecular systems has arisen from advances in genome-wide measurement and applications of such models in biotechnology and synthetic biology. In particular, genome-scale models of cellular metabolism beyond the steady state are required in order to represent transient and dynamic regulatory properties of the system. Development of such whole-cell models requires new modelling approaches. Here, we propose the energy-based bond graph methodology, which integrates stoichiometric models with thermodynamic principles and kinetic modelling. We demonstrate how the bond graph approach intrinsically enforces thermodynamic constraints, provides a modular approach to modelling, and gives a basis for estimation of model parameters leading to dynamic models of biomolecular systems. The approach is illustrated using a well-established stoichiometric model of Escherichia coli and published experimental data.

由于全基因组测量的进步以及此类模型在生物技术和合成生物学中的应用，人们对生物分子系统的动态模拟模型重新产生了兴趣。特别是，需要超出稳态的细胞代谢的基因组规模模型，以表示系统的瞬态和动态调节特性。这种全细胞模型的开发需要新的建模方法。在这里，我们提出了基于能量的键图方法，该方法将化学计量模型与热力学原理和动力学建模相结合。我们演示了键图方法如何从本质上强制执行热力学约束，提供建模的模块化方法，并为估计导致生物分子系统动态模型的模型参数提供基础。大肠杆菌和已发表的实验数据。