TY - JOUR T1 - Steady-State Kinetic Modeling Constrains Cellular Resting States and Dynamic Behavior A1 - Purvis, Jeremy E. A1 - Radhakrishnan, Ravi A1 - Diamond, Scott L. Y1 - 2009/03/06 N2 - Author Summary Cells respond to extracellular signals through a complex coordination of interacting molecular components. Computational models can serve as powerful tools for prediction and analysis of signaling systems, but constructing large models typically requires extensive experimental datasets and computation. To facilitate the construction of complex signaling models, we present a strategy in which the models are built in a stepwise fashion, beginning with small “resting” networks that are combined to form larger models with complex time-dependent behaviors. Interestingly, we found that only a minor fraction of potential model configurations were compatible with resting behavior in an example signaling system. These reduced sets of configurations were used to limit the search for more complicated solutions that also captured the dynamic behavior of the system. Using an example model constructed by this approach, we show how a cell's resting behavior adjusts to changes in the kinetic rate processes of the system. This strategy offers a general and biologically intuitive framework for building large-scale kinetic models of steady-state cellular systems and their dynamics. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 5 IS - 3 UR - https://doi.org/10.1371/journal.pcbi.1000298 SP - e1000298 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1000298 ER -