This brief demo illustrates the simulation of "generic" nucleotide binding, kinase and phosphatase reactions using the reaction generators in the "modKinase" module.
The nucleotide binding reaction generators produce reactions for binding and unbinding of proteins to nucleotides like ATP, ADP, GTP, etc. When one of these small molecules binds to, say, a kinase, its bound form is represented as a modification of the kinase, which must be a mod-mol. When the nucleotide unbinds, it is again represented as a molecule, usually a "featureless" stoch-species.
The kinase reaction generators make reactions in which complexes containing a kinase mod-mol act on complexes containing an appropriate substrate mod-mol to phosphorylate the substrate mod-mol within its complex. This phosphorylation reaction is modeled as an ordinary binary reaction; there is not a separate step in which the kinase binds its substrate. The substrate mod-mol can admit phosphorylation at more than one phosphorylation site.
The phosphatase generator make reactions in which a "featureless" phosphatase, modeled as a stoch-species, dephosphorylates complexes containing a given substrate mod-mol. The generator will make reactions for multiple phosphorylation sites on the substrate. The dephosphorylation reactions are modeled as simple binary reactions between the phosphatase and complexes containing the substrate mod-mol.
This plot shows the most interesting aspects of the demo, in which the kinase is present at the beginning as a "singleton" complex just containing the kinase mod-mol "test-kinase." The substrate mod-mol, called "test-substrate," forms a complex with another mol, just called "foo." The substrate has three phosphorylation sites,1, 2 and 3. The first two phosphorylation sites, 1 and 2 are acessible to (phosphorylated by) the kinase. Only the first phosphorylation site can be dephosphorylated by the phosphatase, which is introduced 1 second into the simulation.
The traces starting with "complex" show the sub-populations of the test-kinase:foo complex with test-kinase in different phosphorylation states. Since the kinase never phosphoryates the third site on the substrate, we see that the "complex-3-phos" trace, which shows any of the test-kinase:foo complexes in which the third site is phosphorylated, is flat at population 0.
The trace "complex-1-only-phos" shows the complexes in which the first phosphorylation site is bound, but neither of the other two. Similarly, "complex-2-only-phos" shows the complexes in which the second phosphorylation site is bound, but neither of the other two. Note that, after the phosphatase is added, the "complex-1-only-phos" trace begins to drop, but not "complex-2-only-phos," due to the fact that the phosphatase only dephosphorylates the first modification site.
The remaining plots are less interesting, but do illustrate some worthwhile points. In the following, we see the kinase in its three possible nucleotide binding states: unbound, bound to ATP, and bound to ADP. The next one at least shows that the binding between the nucleotide and the kinase are very tight, since the unbound form barely appears. The kinase starts out "ATP-free," but quickly binds ATP.
The final plot shows the economy of ATP, ADP, and phosphate. The interesting points here are that phosphate only appears after the introduction of the phosphatase and that there is no "metabolic" reaction to convert ADP and phosphate back into ATP. Note also the rapid initial binding of ATP to the kinase.
