  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.
