Step 1

STEP 1: Formulating Your Hypothesis As A ProcessDB Diagram

Biological diagrams represent molecules and molecular complexes in a variety of physiological places or locations. These diagrams also indicate the processes that transport molecules from one location to another, the biochemical processes that transform molecules, and the binding processes that form homo- or heteromultimers from individual molecules. All of these features are easily captured in ProcessDB diagrams.

Add the physiological places to your diagram. Click the Places tab in the database pane. Click the new place icon and enter the name of the place you want to add to your model. Places are the physiological locations of your molecules and molecular complexes. Examples are cytoplasm, plasma membrane, ER lumen, extracellular space, blood plasma. A place is the answer to the question, “Where is this molecule located in the system I am studying”? You can add all your places immediately or add them as you need them. Notice that molecules and complexes may be present in more than one place.

If the place name you chose is already in the ProcessDB database you can use it to build your own diagram; if it is not already in the database, your name will be added to the place list. In either case your place will be highlighted in the place list and you can now drag it onto the diagram pane. For example, if you type Cytoplasm and then drag the name from the database pane to the diagram pane you will see a yellow rectangle named Cytoplasm added to your diagram.

Hint: It is sometimes useful to define places that you might not ordinarily think of as places. For example, if you want to model a molecular complex whose composition changes with time, it can be very helpful to define that complex as a "place". This allows you to add the various molecular constituents to that complex and have the relative abundances of these constituents change with time. A good example of this is a plasma lipoprotein, like the famous HDL or LDL. These are the vehicles carrying lipids in the blood. They are composed of a phospholipid-cholesterol surface monolayer and a neutral lipid (triglyceride and cholesteryl ester) core. By treating LDL as a ProcessDB place it's easy to account for changes in lipoprotein composition with time.

Suppose your theory or hypothesis includes a biochemical reaction. As a specific example we take the degradation of cAMP to AMP. Click the Molecules and Complexes tab. Type cAMP in the search box on the Molecules and Complexes tab. Notice it’s already in the database and ready for you to use. Drag cAMP into the light yellow Cytoplasm place. By the way, if cAMP had not been in the database you could have used the new molecule icon () to add it. Now your screen looks like this:

Notice that the tree structure pane in the lower left of the screen now shows a state called cAMP in Cytoplasm. A State in ProcessDB is a molecule or molecular complex in a particular place. Next find AMP in the molecule list either by scrolling or by typing AMP in the search box. Then drag AMP into the cytoplasm. This yields:

Now we are ready to add the process that converts cAMP to AMP. In ProcessDB all processes and control mechanisms are added to the diagram using the Connect tool () on the diagram pane toolbar. Select the connect tool. Now drag from the substrate to the product. A dialog appears with a default name for this process. You can accept this name or type cAMP phosphodiesterase to rename it. Next click one of the layout buttons () to produce a hierarchical, symmetric or orthogonal layout of the current diagram. ProcessDB takes care of layout automatically even for extremely complex diagrams. Here’s the result:

Suppose you also wish to represent a transport process such as cAMP secretion into the extracellular space. On the place tab scroll or search for Extracellular space. Drag this place onto the diagram. Then drag, from the Molecules and Complexes tab, cAMP into the extracellular space. Finally select the Connect tool and drag from cAMP in Cytoplasm to cAMP in Extracellular space. Click one of the Layout tool buttons to arrange the result neatly.

Suppose you want to add binding of cAMP to a cyclic AMP receptor in the plasma membrane. In the Places tab of the database pane scroll or search for plasma membrane and drag this place to the gray region between the extracellular space and the cytoplasm. This placement is not in any way necessary but it does make the diagram more like the cell.