"Modeling combinatorial complexity of signal transduction systems"
Signal transduction systems are complex for combinatorial reasons: during signaling, a protein may occupy a number of phosphoforms, and it may interact with multiple binding partners, such that proteins combine dynamically to form various heterogeneous complexes. The known interactions and activities of signaling molecules imply hundreds to thousands of possible molecular species even for cases that involve only a few proteins. We have developed an approach and software for modeling the dynamics of a signal transduction system that allows one to account comprehensively and precisely for the possible molecular species implied by specified interactions, activities, and modifications of the molecules in a system (http://cellsignaling.lanl.gov/bionetgen/). Analysis of such detailed models allows to identify the molecular species, reactions and pathways that are prevalent during signaling, and to investigate different assumed signaling mechanisms. Such models are relevant for rational drug discovery, analysis of proteomic data, and mechanistic studies of signal transduction system.