Computational Modeling of Signal Transduction Networks: A Pedagogical Exposition
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We give a pedagogical introduction to computational modeling of signal transduction networks, starting from explaining the representations of chemical reactions by differential equations via the law of mass action. We discuss elementary biochemical reactions such as Michaelis–Menten enzyme kinetics and cooperative binding, and show how these allow the representation of large networks as systems of differential equations. We discuss the importance of looking for simpler or reduced models, such as network motifs or dynamical motifs within the larger network, and describe methods to obtain qualitative behavior by bifurcation analysis, using freely available continuation software. We then discuss stochastic kinetics and show how to implement easy-to-use methods of rule-based modeling for stochastic simulations. We finally suggest some methods for comprehensive parameter sensitivity analysis, and discuss the insights that it could yield. Examples, including code to try out, are provided based on a paper that modeled Ras kinetics in thymocytes.
