1. M. Chaves, R.J. Dinerstein, and E.D. Sontag. Optimal length and signal amplification in weakly activated signal transduction cascades. J. Physical Chemistry, 108:15311-15320, 2004. [PDF] Keyword(s): systems biology, biochemical networks, dynamical systems. Abstract:

   Weakly activated signaling cascades can be modeled as linear systems. The input-to-output transfer function and the internal gain of a linear system, provide natural measures for the propagation of the input signal down the cascade and for the characterization of the final outcome. The most efficient design of a cascade for generating sharp signals, is obtained by choosing all the off rates equal, and a "universal" finite optimal length.




2. M. Chaves, E.D. Sontag, and R. J. Dinerstein. Steady-states of receptor-ligand dynamics: A theoretical framework. J. Theoret. Biol., 227(3):413-428, 2004. [PDF] Keyword(s): zero-deficiency networks, systems biology, biochemical networks, receptor-ligand models, dynamical systems. Abstract:

   This paper studies aspects of the dynamics of a conventional mechanism of ligand-receptor interactions, with a focus on the stability and location of steady-states. A theoretical framework is developed, and, as an application, a minimal parametrization is provided for models for two- or multi-state receptor interaction with ligand. In addition, an "affinity quotient" is introduced, which allows an elegant classification of ligands into agonists, neutral agonists, and inverse agonists.

1. M. Chaves, E.D. Sontag, and R.J. Dinerstein. Gains and optimal design in signaling pathways. In Proc. IEEE Conf. Decision and Control, Paradise Island, Bahamas, Dec. 2004, IEEE Publications, pages 596-601, 2004. Keyword(s): systems biology, biochemical networks, dynamical systems.

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