As we have seen in Chap. 2 , making a model for a synthetic gene circuit demands to define the species and the reactions necessary to predict the dynamics of the circuit output. The circuits we dealt with so far were structurally simple since they contained a handful of transcription units and their models could be derived by hands. However, genetic circuits made of a high number of DNA components – such as the RNAi-based logic evaluator  described in this Chapter – require computational methods in order to determine, in an automatic way, all reactions and species to be considered in their models. Rule-based modeling is a powerful computational technique that permits to derive model species and reactions from a minimal, abstract description of the kind of molecules involved in a biological system and the way they interact. In this Chapter we will give an introduction to the main ideas of rule-base modeling, and we will show how to derive fully mechanistic models for both the Repressilator and the Toggle Switch by using the open-source software BioNetGen .
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