title: Modular bond-graph modelling and analysis of biomolecular systems.
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 study suggests that they can play the same rôle 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 mitogen-activated protein kinase cascade (Raf-MEK-ERK pathway) is used as an illustrative example.
authors.affiliation: Centre for Systems Genomics, University of Melbourne, Victoria 3010, Australia. peter.gawthrop@unimelb.edu.au.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gawthrop
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science, Melbourne School of Engineering, University of Melbourne, Victoria 3010, Australia.
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Crampin
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry; D000465:Algorithms; D002384:Catalysis; D053263:Gene Regulatory Networks; D030342:Genetic Diseases, Inborn / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010710:Phosphates / Q000737:chemistry; D010766:Phosphorylation; D015398:Signal Transduction; D049490:Systems Biology; D013816:Thermodynamics
chemical_list: D010710:Phosphates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D020928:Mitogen-Activated Protein Kinases