Automated Layer Construction (ALC) - Tutorial

In this tutorial, we exemplify automated modeling for a small example system. Assume a receptor R that can bind the ligand L. We consider one additional binding site which undergoes autophosphorylation and is influenced by the state of the ligand binding site. Therefore, a graded interaction [1] is present between the processes of ligand binding and autophosphorylation. An effector E can bind to the phosphorylated binding site on the receptor R which leads to a receptor-effector complex RXE. For steric reasons, the binding of E protects the binding site on R from dephosphorylation, while E can only bind if the binding site is phosphorylated. This means that an all-or-none interaction [1] is present between the processes of binding site phosphorylation and effector binding. The phosphorylated receptor can phosphorylate E that is bound to other receptors. Free E can only be dephosphorylated. Therefore, a graded interaction is present between the processes of effector binding and effector phosphorylation. Free and unphosphorylated E is degraded and synthesized. We do not consider synthesis or degradation of the receptor. Note that this example system is very similar to the example system in the manuscript and additionally includes phosphorylation of the effector, as well as synthesis and degradation of free unphosphorylated E. Layer-based modularization, according to the interaction graph of the ligand binding, receptor phosphorylation, effector binding and effector phosphorylation processes is shown in Figure 1.