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Abstract

Protein domains are the basic units of signalling processes. The mechanisms they are involved in usually follow recurring patterns, such as phosphorylation / dephosphorylation cycles. In this contribution, a set of common motifs was defined and their dynamic models were analysed with respect to number and stability of steady states. In a first step Feinberg's Chemical Reaction Network Theory was used to determine whether a motif can show multistationarity or not. The analysis revealed that, apart from double-step activation motifs including a distributive mechanism, only those motifs involving an autocatalytic reaction can show multistationarity. To further characterise these motifs, a large number of randomly chosen parameter sets leading to bistability was generated, followed by a bifurcation analysis for each parameter set and a statistical evaluation of the results. The statistical results can be used to explore robustness against noise, pointing to the observation that multistationarity {at the single-motif level} may not be a robust property: the range of protein concentrations compatible with multistationarity is fairly narrow. Furthermore, experimental evidence suggests that protein concentrations vary substantially between cells. Considering a motif designed to be a bistable switch, this implies that fluctuation of protein concentrations between cells would prevent a significant proportion of motifs to act as a switch. We consider this work as a first step towards a catalogue of fully characterised signalling modules. copyright: The Institution of Engineering and Technology 2008 [accessed 2013 June 14th]