Our latest paper, which has just appeared online in the Journal of Theoretical Biology, considers how to build simplified, yet physically plausible mathematical models of complex biological systems. Our aim is to help speed up development of whole-cell models – i.e. virtual cell models which simulate all underlying biochemical processes occurring in a cell. To achieve this it is necessary to adopt a modular approach, in which different components are modelled individually and are subsequently assembled into a model of the whole system. For this to work these model components have to ‘play nicely’ with each other. One way to ensure that model components are compatible, and will plug together into a functioning composite model, is to require them to conform to basic physical conservation principles and thermodynamic consistency.
At the same time, however, to construct whole-cell models we also need simplified representations which capture essential biophysical features while avoiding unnecessarily complexity. In our new paper, using energy generation in the mitochondrial electron transport chain as an example, we demonstrate an approach to developing simplified but thermodynamically consistent models (which we call ‘physically-plausible’ models). We show that these physically-plausible models behave like the full system and can readily be incorporated into large scale biochemical simulations, without the requirement of full mechanistic simulation of the underlying biochemical processes. We think this is a significant step towards a modular and multi-scale framework for the development of genome-scale whole-cell models.
P.J. Gawthrop, P. Cudmore, E.J. Crampin
Physically-Plausible Modelling of Biomolecular Systems: A Simplified, Energy-Based Model of the Mitochondrial Electron Transport Chain
Journal of Theoretical Biology