ModelBricks Construction

The original model

The creation of ModelBricks begins with a full model. As an example, we can take this model of a Rho GTPase cycle, which was published by Ota et al. in 2015 (PMID: 25628036).
SBGN visualization
Figure 1B from publication
In this publication, the authors are investigating possible positive regulation of Rho GTPase activity by RhoGDIs. The SBML file provided in the publication was first imported into VCell. Simulations were run in VCell and confirmed to replicate those from the publication. As the concentration of intracellular free GDIs increases, Rho activation is prolonged, despite the overall decrease in Rho activity over time.
Simulation: Publication
Figure 2B
VCell: Simulation

Annotating the model

VCell reaction diagram
The model was then fully annotated to give the viewer a more thorough understanding of the model. Both textual and database annotations were added.
Annotation of original model in VCell
Species were modified so that they were constructed of individual molecules. By completing this step, each species became much more comprehensive and the constituent parts were clearly displayed.
Species composed of individual molecules

ModelBrick creation

The first ModelBrick derived from the full model describes the activation of GEF and the degradation of the activator. The remaining portion of the model is its own ModelBrick, but it was further broken into two additional ModelBricks as well.
The two additional ModelBricks were created with one of them describing a much simpler Rho GTPase cycle and the other describing complex formation with GDIs and G proteins. All ModelBricks are independent entities that can be combined to construct full models that are fully annotated and computable.