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As a result, the number of chemical species that can be populated in a cell signaling network, and hence the number of equations in an ordinary differential equation model required to capture the dynamics of these species, is prohibitively large. To overcome this problem, the rule-based modeling approach has been developed for representing interactions within signaling networks efficiently and compactly through coarse-graining of the chemical kinetics of molecular interactions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Here, we provide a demonstration that the rule-based modeling approach can be used to specify and simulate a large model for ERBB receptor signaling that accounts for site-specific details of protein-protein interactions. The model is considered large because it corresponds to a reaction network containing more reactions than can be practically enumerated. The model encompasses activation of ERK and Akt, and it can be simulated using a network-free simulator, such as NFsim, to generate time courses of phosphorylation for 55 individual serine, threonine, and tyrosine residues. The model is annotated and visualized in the form of an extended contact map.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>With the development of software that implements novel computational methods for calculating the dynamics of large-scale rule-based representations of cellular signaling networks, it is now possible to build and analyze models that include a significant fraction of the protein interactions that comprise a signaling network, with incorporation of the site-specific details of the interactions. Modeling at this level of detail is important for understanding cellular signaling.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-6-107","type":"journal-article","created":{"date-parts":[[2012,8,22]],"date-time":"2012-08-22T10:14:56Z","timestamp":1345630496000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Specification, annotation, visualization and simulation of a large rule-based model for ERBB receptor signaling"],"prefix":"10.1186","volume":"6","author":[{"given":"Matthew S","family":"Creamer","sequence":"first","affiliation":[]},{"given":"Edward C","family":"Stites","sequence":"additional","affiliation":[]},{"given":"Meraj","family":"Aziz","sequence":"additional","affiliation":[]},{"given":"James A","family":"Cahill","sequence":"additional","affiliation":[]},{"given":"Chin Wee","family":"Tan","sequence":"additional","affiliation":[]},{"given":"Michael E","family":"Berens","sequence":"additional","affiliation":[]},{"given":"Haiyong","family":"Han","sequence":"additional","affiliation":[]},{"given":"Kimberley J","family":"Bussey","sequence":"additional","affiliation":[]},{"given":"Daniel D","family":"Von Hoff","sequence":"additional","affiliation":[]},{"given":"William S","family":"Hlavacek","sequence":"additional","affiliation":[]},{"given":"Richard G","family":"Posner","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2012,8,22]]},"reference":[{"key":"954_CR1","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/nature01254","volume":"420","author":"H Kitano","year":"2002","unstructured":"Kitano H: Computational systems biology. 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