Modular Bond-graph Modelling and Analysis of Biomolecular Systems

TL;DR

This paper demonstrates how bond graphs can be used to model, analyze, and synthesize biomolecular systems in a thermodynamically consistent way, revealing feedback, modularity, and retroactivity effects.

Contribution

It introduces a bond graph framework for biomolecular systems, establishing their structure, and explores modularity, feedback, and retroactivity within this context.

Findings

Bond graphs model biomolecular thermodynamics accurately.

Modularity concepts help in understanding system behavior.

Power supply reduces retroactivity in modules.

Abstract

Bond graphs can be used to build thermodynamically-compliant hierarchical models of biomolecular systems. As bond graphs have been widely used to model, analyse and synthesise engineering systems, this paper suggests that they can play the same role in the modelling, analysis and synthesis of biomolecular systems. The particular structure of bond graphs arising from biomolecular systems is established and used to elucidate the relation between thermodynamically closed and open systems. Block diagram representations of the dynamics implied by these bond graphs are used to reveal implicit feedback structures and are linearised to allow the application of control-theoretical methods. Two concepts of modularity are examined: computational modularity where physical correctness is retained and behavioural modularity where module behaviour (such as ultrasensitivity) is retained. As well as providing computational modularity, bond graphs provide a natural formulation of behavioural modularity and reveal the sources of retroactivity. A bond graph approach to reducing retroactivity, and thus inter-module interaction, is shown to require a power supply such as that provided by the ATP = ADP + Pi reaction. The MAPK cascade (Raf-MEK-ERK pathway) is used as an illustrative example.