Additional file 1.

Stochastic pi-calculus model of the biochemical interactions involved in the EGFR signalling pathways. The model is based on the reaction map of Figure 1. Essentially, each connected graph represents the set of possible states of a given protein, where each node represents a protein in a particular state. For example, in the top right there are three graphs for proteins Phase1, Phase2 and Phase3, where each of these proteins can be in two possible states, bound or free. Proteins can change their state by interacting with each other over shared channels, where each labelled edge represents an action that a protein can perform in order to change from its current state to a new state. For example, the protein Phase1 can become bound by interacting on channel phase1, and can then become free by interacting on channel p. The channel phase1 is parameterised by p, written phase1(p). This indicates that the protein becomes bound on p after the interaction takes place. In this figure we have grouped sets of proteins together into subsystems, denoted by rectangular boxes. For example, in the top right we have grouped the proteins Phase1, Phase2, Phase3, Raf, MEK and ERK into a cascade subsystem. All the channels inside a given subsystem are local to that subsystem, apart from those that are represented between boxes. For example, in the cascade subsystem the channels phase1, phase2 and phase3 are local and cannot interact with any of the other subsystems, while channels rasgtp and erkpp can interact with two other subsystems. This gives an overall schematic for the interactions between the various subsystems. We observe that the ERK subsystem can interact with the Grb2 subsystem on channel erkpp. Similarly, the EGF subsystem can interact with the Grb2 subsystem on channel complex, representing the EGF-EGFR'2-GAP complex. Finally, we observe that the RasGTP subsystem can interact with both the cascade and the Grb2 subsystem. Note that the interactions with RasGTP are parameterised by channels r, r' and rd, indicating that the bound RasGTP protein can unbind in three different ways, resulting in RasGTP, RasGTP' or RasGDP. A corresponding set of chemical reactions can be automatically generated for the entire system, but note that the translation does not preserve the modular description of the system. The model is available at http://research.microsoft.com/en-us/um/people/aphillip/egfr09/ webcite and the SPiM simulator is available at http://research.microsoft.com/spim/ webcite

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Wang et al. BMC Systems Biology 2009 3:118   doi:10.1186/1752-0509-3-118