Defining transitions of the myosin heads

After defining all the states, you will define the transition rules between the states. Here let us define the transitions shown below. Each orange box represents a molecule which binds with the myosin head or dissociates from the myosin head at the associated transition. "Pi" represents phosphoric acid, "ATP" represents adenosine triphosphate, and "ADP" represents adenosine diphosphate. The notations "fa", "fb", "hf", "hb" and "g" are the transition rates. They mean how many times these transitions take place in a second.

Connecting the states by the transition paths

Click on the green square button in the state box P_XB and hold the mouse button to start connecting from P_XB to XB_PreR.

Then drag the orange arrow to the state box XB_PreR and release the mouse button.

In a similar manner, add connections from XB_PreR to P_XB, from XB_PreR to XB_PostR, from XB_PostR to XB_PreR and from XB_PostR to P_XB. ID numbers are automatically given by XB Modeler and you do not have to care for them.

Defining the transition rate parameters

Now you will prepare to give transition rates to the paths. It is convenient to utilize Your Custom Parameter for modifying the transition rates according to your simulation results later on.

Click Edit Parameters in the menu bar.

Click on the Your Custom Parameter tab.

Define the parameters in the Your Custom Parameter form. Then click on the Close button.

Defining the transition rates

Now you will give a transition rate to each path by using the parameters.

Click on the arrow from P_XB to XB_PreR.

Click on the Define a rate button.

Define the rate "r" in the Transition dialog. Here "r" is the transition rate that means how many times this transition occurs in a second on average. "fa" is the parameter that you have defined in the Your Custom Parameter form.

Click on the Close button. Now you have finished the definition of the transition rate from P_XB to XB_PreR.

In a similar way, define the transition from XB_PreR to P_XB as “r=fb” where “fb” is the parameter that you have defined in the Your Custom Parameter form.

Now you will define the transition from XB_PreR to XB_PostR that is accompanied with the myosin head rotation and the Pi molecule release.

Click on the arrow from XB_PreR to XB_PostR, and then click on the Define a rate button. Click on the Myosin head stroke check box to tell XB Modeler that this transition is accompanied with the myosin head rotation, and enter “9” for the Myosin head stroke distance [nm] (X_STROKE). This means that XB Modeler increments the arm stretch by X_STROKE when this transition occurs. Click on the Pi release check box to tell XB Modeler that this transition is accompanied with the Pi molecule release. Finally, define the transition rate as “r = hf” in the Transition dialog, where “hf” is the parameter defined in the Your Custom Parameter form, and then click on the Close button.

In a similar way, you will define the transition from XB_PostR to XB_PreR that is accompanied with the myosin head backward rotation and the Pi molecule binding.

Click on the arrow from XB_PostR to XB_PreR, and then click on the Define a rate button. Click on the Myosin head stroke check box to tell XB Molder that this transition is accompanied with the myosin head rotation, and enter “-9” for the Myosin head stroke distance [nm] (X_STROKE). This means that XB Modeler increments the arm stretch by X_STROKE when this transition occurs. Here the minus value of X_STROKE implies a backward head rotation. Click on the Pi binding check box to tell XB Modeler that this transition is accompanied with the Pi molecule binding. Finally, define the transition rate as “r = hb” in the Transition dialog, where “hb” is the parameter defined in the Your Custom Parameter form, and then click on the Close button.

Finally, you will define the transition from XB_PostR to P_XB that is accompanied with the myosin head dissociation from the actin filament, the ADP molecule release and the ATP molecule binding. Click on the arrow from XB_PostR to P_XB, and then click on the Define a rate button. Click on the ADP release check box and the ATP binding check box to tell XB Modeler that this transition is accompanied with the ADP molecule release and ATP molecule binding. Finally, define the transition rate as “r = g” in the Transition dialog, where “g” is the parameter defined in the Your Custom Parameter form, and then click on the Close button. Now you have finished constructing the three state model.