Instruction
for CADLIVE Simulator
Example:
E. coli heat shock response system
TPP steadystate analysis
CONVERSION
Contents
3.
Upload of data for regulatorreaction equations
4.
Selection of conversion methods
5.
Editing Mathematical Model (DAEs)
NOTICE
If there is anything wrong with calculation and you want to kill your job, access the site of http://kurata01.bse.kyutech.ac.jp/TEST/Life/kill, and push the kill simulator button.
Following
the installation of the CADLIVE Simulator, open http://kurata01.bse.kyutech.ac.jp/TEST/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 TPP_RAPID.
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 gSteadystateh as analysis type.
Fig. 61Selection of analysis type
As "Analsys type", users can choose either gDynamich or gSteadystateh. g Dynamich 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.
Set values for
NewtonRaphson Method. 

Maximum trial times 
20 
Tolerance for convergence of functions 
1e12 
Tolerance for convergence of variables 
1e12 
Ratio of changing parameters 
1.1 
Change width for calc. sensitivity (STD) 
0.001 
Other 

Gvalue 
1.0 
Y default value 
0.01 
Change
width for calc. sensitivity (STD) means the ratio of the change in the kinetic
parameters to their values, which is used to calculate the sensitivity of the
dependent variables (concentrations) to the change in the kinetic parameters.
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 (TPP_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 results of the steady state concentrations and the sensitivity are shown in Fig. 91. 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 steady state concentrations can be saved for the subsequent analysis (Ssystem analysis, simulation of DAEs). This [Initial val.] button will be not displayed when parameter survey has been carried out.
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 the steady state concentrations, and a series of sensitivity 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