The linear framework uses finite, directed graphs with labelled edges to model biomolecular systems. Graph vertices represent biochemical species or molecular states, edges represent reactions or transitions and labels represent rates. The graph yields a linear dynamics for molecular concentrations or state probabilities, with the graph Laplacian as the operator, and the labels encode the nonlinear interactions between system and environment. The labels can be specified by vertices of other graphs or by conservation laws or, when the environment consists of thermodynamic reservoirs, they may be constants. In the latter case, the graphs correspond to infinitesimal generators of Markov processes. The key advantage of the framework has been that steady states are determined as rational algebraic functions of the labels by the Matrix-Tree theorems of graph theory. When the system is at thermodynamic equilibrium, this prescription recovers equilibrium statistical mechanics but it continues to hold for non-equilibrium steady states. The framework goes beyond other graph-based approaches in treating the graph as a mathematical object, for which general theorems can be formulated that accommodate biomolecular complexity. It has been particularly effective at analysing enzyme-catalysed modification systems and input-output responses.
Keywords: Hill functions; Hopfield barrier; gene regulation; graph theory; linear framework; post-translational modification systems; rational parametrization.
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