Rule-based modeling for protein-protein interaction networks-the Cyanobacterial circadian clock as a case study

Heinz Koeppl, Marc Hafner, Vincent Danos

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Rule-based modeling is a new approach to cope with the inherent combinatorial complexity in protein-protein interaction networks, such as cellular signaling pathways. In contrast to reactions that act on chemical species, rules can act on partially specified species. A single rule can thus account for multiple reactions and reflects the limited local context on which most protein-protein interaction events are conditioned on. The cyanobacterial circadian clock is purely protein-based and is centered around the cyclic phosphorylation of the hexameric KaiC protein. Its different phosphorylation states give rise to a combinatorial number of species that would be required for a traditional description. We give a detailed rule-based model, incorporating recent experimental findings of twosite phosphorylation and monomer exchange of the KaiC hexamer. Monte-Carlo sampling of kinetic parameters shows that monomer exchange alone may not be sufficient to synchronize the KaiC hexamers.
Original languageEnglish
Title of host publicationInternational Workshop on Computational Systems Biology 2009
Pages87-90
Number of pages4
Publication statusPublished - 2009

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