Mass fluctuation kinetics: analysis and computation of equilibria and local dynamics

The mass fluctuation kinetics (MFK) model is a set of coupled ordinary differential equations approximating the time evolution of means and covariances of species concentrations in chemical reaction networks. It generalises classical mass action kinetics (MAK), in which fluctuations around the mean are ignored. MFK may be used to approximate stochasticity in system trajectories when stochastic simulation methods are prohibitively expensive computationally. This study presents a set of tools to aid in the analysis of systems within the MFK framework. A closed-form expression for the MFK Jacobian matrix is derived. This expression facilitates the computation of MFK equilibria and the characterisation of the dynamics of small deviations from the equilibria (i.e. local dynamics). Software developed in MATLAB to analyse systems within the MFK framework is also presented. The authors outline a homotopy continuation method that employs the Jacobian for bifurcation analysis, that is, to generate a locus of steady-state Jacobian eigenvalues corresponding to changing a chosen MFK parameter such as system volume or a rate constant. This method is applied to study the effect of small-volume stochasticity on local dynamics at equilibria in a pair of example systems, namely the formation and dissociation of an enzyme-substrate complex and a genetic oscillator. For both systems, this study reveals volume regimes where MFK provides a quantitatively and/or qualitatively correct description of system behaviour, and regimes where the MFK approximation is inaccurate. Moreover, our analysis provides evidence that decreasing volume from the MAK regime (infinite volume) has a destabilising effect on system dynamics.