Instruction
for CADLIVE Simulator
Example:
E. coli heat shock response system
CMA CONVERSION
Contents
3.
Upload of data for regulatorreaction equations
4.
Selection of conversion methods
5.
Editing Mathematical Model (CMA)
11
Calculation of the initial values for DAEs (TPP)
11.1 Saving the final points of CMA
simulation
11.2 Conversion of the final concentration of
CMA to the initial concentration for DAEs
NOTICE
If there is anything wrong with calculation and you want to kill your job, access the site of http://kurata23.bio.kyutech.ac.jp/Life/kill, and push the kill simulator button.
The problem for DAEs is to find the initial values that are necessary for solving their algebraic equations. We suggest that the steady state concentration of CMA with rapid equilibrium approximation is very close to those of DAEs. This instruction presents how one makes the initial values for DAEs from CMA simulation.
Following
the installation of the CADLIVE Simulator, open http://kurata23.bio.kyutech.ac.jp/Life/index.html@on a PC browser to display the screen(Fig. 11). Input the user name,
subsequently his/her password to start up simulation.
Fig. 11 Login
screen
Clicking the "Simulator" button on the left hand side (Fig. 21) changes the upper region of the screen, as shown in Fig.22
Fig. 21Startup menu
Clicking the [Regulatorreaction equations] button (Fig. 22) displays the new screen. Select the XML data file for the regulatorreaction equations (HSR_demo.xml) from usersf PC (Fig. 31). The data file should be described by using the CADLIVE Editors. Users are required to click the buttons within the screen of CADLIVE, not to carelessly click those of the browser.
Fig.
31 Upload of a regulatorreaction equation file from a PC
The table that indicates the selected regulatorreaction equations appears on the screen (Fig. 41). Users choose the conversion method with respect to geneprotein layer, because the heat shock response does not contain the metabolic layer. Select CMA.
Fig. 41
Selection of conversion methods
Following
the selection of the conversion method, clicking the [Confirm] button displays
the confirmation screen (Fig. 42) that is similar to Fig. 41.
Fig. 42
Confirmation screen for the regulatorreaction equations
Clicking the [Submit] button on the confirmation screen (Fig. 42) parses the regulatorreaction equations, converting them into the mathematical model according to the selected conversion method. The resultant mathematical model is displayed as shown in Fig. 51.
Fig. 51 Mathematical model that is obtained from regulatorreaction equations
This screen mainly has seven parts: the header, the definition of constant players, the definition of variables, the definition of the employed parameter labels, the definition of kinetic parameters, the definition of intermediate mathematical expressions, the definition of algebraic equations, and the definition of differential equations.
Clicking the [Regulatorreaction eqs.] button displays another window that shows regulatorreaction equations. Clicking the [Parameter info.] button shows the parameter information. The [Download] button enables users to download various data files to their local PC.
Clicking the [Confirm] button displays the confirmation screen (Fig. 52) that is similar to Fig. 51. If there is no problem, click the [Submit] button.
Fig. 52 Confirmation screen for a mathematical model
Clicking the [Submit] button on the confirmation screen displays the screen (Fig. 61), where users select the method for numerical simulation. Select gDynamich as analysis type.
Fig. 61Selection of analysis type
As "Analsys type", users can choose either gDynamich or gSteadystateh. gDynamich simulates the time evolution of the concentrations by calculating DAEs, and gSteadystateh calculates the concentrations at steady state by solving algebraic equations. The checkbox of "Parameter survey" determines if the simulator surveys the parameter space. Checking the checkbox of "Parallel calculation" carries out parallel calculation that employs the Message Passing Interface (MPI). Notice that the checkbox of "Parallel calculation" cannot be selected prior to checking the parameter survey.
Clicking
the [Submit] button on the screen for selecting analytical type displays the
screen for input of the control data (Fig. 71). Here, input the data, as
provided by the following table
Solver Type
(tolerance) 

NDF 
relative: 1e12 absolute 0.000001 
Set time span and
time stepsize. 

Start time 
0 
End time 
100 
(Initial)time stepsize 
0.0001 
Monitoring interval 
1 
Other 

Gvalue 
1.0 
Y default value 
0.01 
Fig. 71 Set control data for simulation
Following data input, clicking the [Confirm] button shows the confirmation screen (Fig. 72).
Fig. 72 Confirmation screen
Following
confirming the control data for simulation, clicking the [Submit] button on the
screen (Fig. 72) displays the new screen (Fig. 81), where users input the
kinetic parameters and initial values.
Fig. 81 Setting parameters and initial values
In this example, we presented the parameters and initial values that well simulated the heat shock response. Click the [Upload & merge File] button to display the screen (Fig. 82).
Fig. 82 Uploading a parameter file from the local PC
The parameter file that has been made (CMA_Param_HSR.txt) should be input in the box of "FileName". Check the box of "Update all" and click the [Submit] button. The parameters and initial values are automatically input into the mathematical model, as shown in Fig. 83
Fig. 83 Uploaded parameters and initial values
Following clicking the [Confirm] button, clicking the [Submit] button (Fig. 84) starts calculation.
Fig. 84 Startup calculation
The resultant time course data are displayed (Fig. 91), which contain the log regarding the calculation time. When simulation fails, the log is shown first, subsequently displaying the input file.
The button of [Save for input] stores the resultant data as the initial values for the subsequent simulation (Fig. 91), which will be obtained by the [Initial val.] button. The concentrations at the final time and the steady state concentrations can be saved for the subsequent analysis of the timeevolution dynamics and the steady state, respectively. The [Initial val.] button will be not displayed when parameter survey has been carried out.
Clicking the [Graph] button, which is displayed when the timeevolution (Dynamic) is successfully simulated, opens the window for visualizing the results.
Fig. 91 Results
The screens for indicating the results (Fig. 91) have the [Registration] button. Clicking the [Registration] button shows the gRegistration to the DBh screen (Fig. 92) that has also the button of [Registration]. Clicking it saves a series of simulation data as a mathematical model in the database.
Fig. 92 Registration of Data in Database
The screen for results (Fig. 92) has the [Download] button. Clicking it displays the download screen (Fig. 93). The clicked files are downloaded to a local PC.
Fig. 93
Download
In the screen (Fig. 91), clicking the [Graph] button displays the window of "Set Graph Data" (Fig. 101).
Fig. 101DSetting graph data
The right hand side of the screen defines the definition of data that will be plotted on a graph, and can indicate five series of labels and expressions. As default, y1 – y5 and y[1] – y[5] are set as labels and expressions, respectively. Empty labels and expressions are not allowed. The variables y[i], calculation symbols +, , X, /, parentheses (,), and time T are allowed to be used for describing the mathematical expression. Here, set y[1], y[2], y[3], y[4], and y[5]. After setting them, clicking the [Submit] button displays the screen (Fig. 102), where the scaling factor and the regions of Xaxis and Yaxis are automatically calculated based on the expression and the minimum/maximum values to visualize the five timeevolution well.
Fig. 102 Setting graph data
Users are able to change the labels, the scaling factors, and the color of the lines. Checking the checkbox of gnot drawh omits its time evolution from the graph. The button [Recalc] recalculates the scaling factors and the regions for the X/Yaxises. The table on the lower screen is set for the X/Yaxises. X indicates time, and Y the concentrations of variables. Clicking the [Draw graph] button (Fig. 102) displays the results of timeevolution data, as shown in Fig. 103.
.
Fig. 103 Graph display
The [No legend] button omits the legends. The [Set details] button is able to change the color of the graph and other graph expressions. Clicking the [Set details] button displays the window (Fig.104). Users can change the style of the graph by inputting the value in the boxes. The values of the graph size and the location of the legends are determined by using pixel units. The location of the legend is determined by the coordinate of the left and upper legend.
Fig. 104 Detailed setting for a graph
The problem for DAEs is to find the initial values that are necessary for solving their algebraic equations. We suggest that the steady state concentration of CMA with rapid equilibrium approximation is very close to those of DAEs. This chapter instructs how one makes the initial values for DAEs from CMA simulation.
After the simulation for time courses for CMA, the button of [Save for input] stores the resultant data as the initial values for the subsequent simulation (Fig. 111, see Fig. 91), which is obtained by the [Initial val.] button.
In Fig. 112, click the [Initial val.] button to show the final points of the previously saved timecourse data, which are very close to steady state (Fig. 112). This button appears only when the initial values are saved in the previous simulation.
Fig. 111 Results of simulation
Fig. 112 Initial concentrations that are the resultant data of the previous simulation.
Open the window for the initial values from previous simulation (Fig. 113). Calculate the total concentrations for specific species (monomer, modified)(Y_START 2530) and add them to the file, which can be employed as the initial values for DAEs that are equivalent to CMA.
Fig. 113 Initial values from previous simulation.
Fig. 114. Addition of the calculated total concentrations for specific species Y_START[2530].