A rule-based model is specified as a set of reaction rules, which are associated with specific rate laws. Given a set of seed species, reaction rules identify those species that have the features required to undergo the transformation from reactants to products specified in the reaction rule. Interactions represented in a reaction rule are independent of features not explicitly indicated in the reaction rule. Thus, multiple species may qualify as reactants in a set of reactions defined by a single reaction rule.
The modeler can define which components and modifications of a molecule or molecular assembly affect a particular chemical transformation, and which do not. Furthermore, the modeler has the ability to account for steric interference, cooperativity, and any other factors that might influence the rate of a reaction. A reaction rule can state, for example, that �any cell-surface monomeric receptor having an available extracellular binding site and any free extracellular ligand can interact and form a ligand�receptor complex; the probability of this interaction depends only on the total numbers of cell-surface monomeric receptors and extracellular ligands and does not depend on the specific state of the receptor cytosolic domain.� In this example, we assume that the state of the cytoplasmic domain of the receptor does not affect ligand�receptor binding, and thus to parameterize all the reactions specified by the ligand�receptor interaction rule requires just two rate constants: on and off rates.
The rule below depicts the EGF receptor with a binding site for egf (l), a second unspecified site (r) and two phosphorylation sites (Y1068 and Y11848) that can be phosphorylated, unphosphorylated, bound or unbound, combining with an EGF molecule with a receptor binding site (r):
Some of the possible reactions generated by this rule are:
