Gawthrop, P.; Pan, M.

Oscillatory behaviour underpins many essential biological functions and energy is required to sustain oscillation. In this paper, energy-based modelling of biochemical systems using the bond graph approach is combined with classical feedback control theory to give a novel approach to the analysis, and potentially synthesis, of biochemical oscillators. It is shown that oscillation is dependent on the interplay between active and passive feedback and this interplay is formalised using classical frequency-response analysis of feedback systems. In particular, the phase margin is suggested as a simple scalar indicator of the presence or absence of oscillations; it is shown how this indicator can be used to investigate the effect of both the structure and parameters of biochemical system on oscillation. It follows that the combination of classical feedback control theory and the bond graph approach to systems biology gives a novel analysis and design methodology for biochemical oscillators. The approach is illustrated using an introductory example similar to the Goodwin oscillator, the Sel\'kov model of Glycolytic Oscillations and the Repressilator.