You can visualize a systems biology model with various levels of detail. One view sketches only the major species and processes. This model is an example of simple gene regulation, where the protein product from translation controls transcription. You could create a more complex model by adding the enzymes, coenzymes, cofactors, nucleotides, and amino acids that are not included in this model. The gene regulation example simplifies the regulatory mechanism by not showing the contributions of RNA polymerase and any cofactors. The protein product from gene expression binds to a regulatory region on the DNA and represses transcription.
Another way of looking at a systems biology model is to list the reactions in a model with the processes they represent.
DNA -> DNA + mRNA (transcription) mRNA -> mRNA + protein (translation) DNA + protein -> DNA_protein (binding) DNA_protein -> DNA + protein (unbinding) mRNA -> null (degradation) protein -> null (degradation)
Drawing the reaction pathways will help you visualize the relationships between reactions and species. In the gene regulation example, as the amount of a protein increases, the protein forms a complex with the gene responsible for its expression, and slows down protein production.
Reaction equations define a systems biology model at the level of detail needed for a software program to simulate the dynamic behavior of the model. The following reactions for transcription, translation, binding, and degradation describe a simple gene-regulating mechanism.
Transcription is where RNApolymerase and cofactors bind with a DNA molecule. The RNApolymerase then moves along the DNA and combines nucleotides to create mRNA. A simple model of transcription shows only the DNA and mRNA.
This model simplifies the transcription and the synthesis of mRNA by using a single reaction.
Reaction: DNA -> DNA + mRNA Reaction rate: v = k1*DNA molecule/second Species: DNA = 50 molecule mRNA = 0 molecule Parameters: k1 = 0.2 1/second
After the mRNA moves from the nucleus to the cytoplasm, it can bind with ribosomes. The ribosomes move along the mRNA and create proteins with the help of tRNAs bound to amino acids. A simple model of translation shows only the mRNA and protein product.
The synthesis of the protein is modeled as a single reaction.
Reaction: mRNA -> mRNA + protein Reaction rate: v = k2*mRNA molecule/second Species: mRNA = 0 molecule protein = 0 molecule Parameters: k2 = 20 1/second
Transcription of DNA to mRNA is regulated by the binding of the protein product from translation to the DNA. As more protein is produced, the DNA is bound with the protein more often and less time is available for transcription with the unbound DNA.
Forward Reaction (Binding)
Reaction: DNA + protein -> DNA_protein Reaction rate: v = k3*DNA*protein molecule/second Species: DNA = 50 molecule protein = 0 molecule Parameters: k3 = 0.2 1/(molecule*second)
Notice how the units are described for the parameter k3. In the literature, some of the common ways to display second-order rate constants are mole-1second-1 or 1/mole-second. However, software evaluations of these common ways are sometimes ambiguous.
Reverse Reaction (Unbinding)
Reaction: DNA_protein -> DNA + protein Reaction rate: v = k3r*DNA_protein molecule/second Species: DNA_protein = 0 molecule Parameters: k3r = 1 1/second
For this tutorial, model the binding and unbinding reactions as one reversible reaction.
Reaction: DNA + protein <-> DNA_protein Reaction rate: v = k3*DNA*protein - k3r*DNA_protein molecule/second Species: DNA = 50 molecule protein = 0 molecule Parameters: k3 = 0.2 1/(molecule*second) k3r = 1 1/second
Protein and mRNA degradation are important reactions for regulating gene expression. The steady-state level of these compounds is maintained by a balance between synthesis and degradation reactions. Proteins are hydrolyzed to amino acids with the help of proteases, and nucleic acids are degraded to nucleotides.
mRNA degradation is modeled as a transformation to the null species.
Reaction: mRNA -> null Reaction rate: v = k4*mRNA molecule/second Species: mRNA = 0 molecule Parameters: k4 = 1.5 1/second
Likewise, protein degradation is also modeled as a transformation to the null species. The species null is a predefined species name in SimBiology® models.
Reaction: protein -> null Reaction rate: v = k5*protein molecule/second Species: protein = 0.0 molecule Parameters: k5 = 1.0 1/second
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