E-CELL2 User's Manual Chapter 5: Creating User Defined Reactor Files [Chapter 1:Chapter 2:Chapter 3:Chapter 4:Chapter 6][Top]

INDEX
 1.Introduction 1.1 Postern Reactor 2.Reactor Description File 2.1 Writing Reactor Description Files Keywords for general information Keywords for the Reactor Spec Sheet Keywords for the Reactor Source Code 2.2 Reactor Description Example 3 Conversion to Reactor Source Code(.C .h file)and DLL 4 Loading the E-CELL2 System 5 General reactors from the E-CELL2 project

# 1 Introduction

In the E-CELL2 System, cellular models can be created with the combination of three object types: Substance (to describe substance amount), Reactor (describe the reaction and the reactor system path), and System (to describe certain functions). Reactor describes the time-change of the Substance amount which plays an essential role under an E-CELL2 model.

Reactor objects can be freely manipulated by the user. Reactor objects must be compiled in separate with the E-CELL2 System and therefore must be converted to a format that E-CELL2 can read; if correctly written, the E-CELL2 System loads up the defined Reactor. For Reactor objects are written in C++, users can create almost any kind of a kinetic model.

Figure: The scheme of files used in E-CELL2 System

The graph above describes the files used in E-CELL2 System. As it can be seen, Reactors are created and compiled in separate of the E-CELL2 System itself. In order to create a Reactor object, the Reactor Description file (RD file) must be written with the actual commands and the required data(such as the equation and the parameters) inside. The RD file gets converted to C++ and .dll modules executable with E-CELL2 System. RD files can also be converted to a Reactor Spec Sheet in Latex format.

## 1.1 Postern Reactor

Two kinds of Reactors exist: Regular Reactors and Postern Reactors. While regular reactors use integrating functions to solve multi-derivative equations, postern reactors are separated from these integrating functions and used in cases where derivative equations are not suitable for calculating the Substance amount. The two reactors realize due to the multi-step calculation architecture; after the React step in the regular reactor is executed, the calculation will be performed in the Postern Step. Postern Reactors can be used in the following case:

• In cases where the substance amount is controlled as discrete. (in cases where the substance amount is very low)
• In cases where the substance amount can be defined directly without the integrating functions. For reactors describing the transcription start point or in cases where all substance value reduce to half because of a mitosis
• In cases the reaction is described as an algebraic function. Suitable for RapidEquilibrium Reactions or for Osmotic Calculations.

While regular reactors calculate the reaction speed in order to define the substance amount, postern reactors do not consider the substance flux and handle all of the substance involved . Thus, while regular reactors use the velocity(Float v)method in performing calculations, postern Reactors use the SetQuantity(Float Q)method in returning calculation results.

Postern reactors have "PReactor" on the end of their name. (ex: "ABCPReactor")

Each postern reactor must and can only handle a single substance where the substance cannot be defined more than once (if so, the simulation accuracy cannot be guaranteed). If multiple reactions effect a single substance, each reactions must be inside a singular postern reactor such as the GeneralRapid EquilibriumPReactor.

# 2 Reactor Description File

Though several General Reactors for simulation is already included in the E-CELL2 System Package (refer to section 5), in order to create non-standard reactions or to perform higher leveled simulations, it is required for the user to create their own Reactor files.

## 2.1 Creating a Reactor Description File

RD files can be created by including the keyword - value pair lines. Note for the following while creating RD files:

• Keywords must be Alphabets (uppercase only) or underbars without spaces.
• Keywords must start with @ or %. While lines that start with @ will simply be included into the target, the lines starting with % will be treated as hash separated by dots (".").
• Keywords that start with "#" will be created as comment lines. In order to use the # character at the start of the line as a non-comment line, use \# or include a space before it. #s at non-starting positions will be treated as normal characters.
• For line headers without these keywords, the line will be treated as continuance from the previous line. (While converting to Spec Sheet, in order to add a new line, type "\\")
• Certain Keywords can be omitted if they are not required.

### General Keywords

• @CLASSNAME:
• @BASECLASS:
• @AUTHOR:
• @EMAIL:
• @DATE:
• %VERSION:
• @BRIEF_DESCRIPTION:

@CLASSNAME line is to define the Reactor Classname. The filename of the Reactor MUST BE CLASSNAME.rd in any case.
@BASECLASS line is to define the base class for that class. In most cases, FluxReactor is defined. @AUTHOR, @EMAIL, @DATE lines are to define those information into the reactor.
@BRIEF_DESCRIPTION line is a single-lined definition of the Reactor. The details of these keywords are passed on to the E-CELL2 System.

### Keywords for the Reactor Spec Sheet

• @DESCRIPTION:
• @EQUATION:
• %SUBSTANCE:
• @NOTES:

@DESCRIPTION line is to define the full description of that Reactor.
@EQUATION line is to define the equation in LaTeX displaymath format. Thus:

1. $$ Write Equation$$
2. \begin{displaymath} Write Equation \end{displaymath}
3. $ Write Equation$

choose any of the above.

%SUBSTANCE line is to define the Substance from Substrate, Product, Catalyst, and Effector, its maximum amount, minimum amount and their comments separated by commas ",". The max/min amounts can be defined in decimal integers, but it is also possible to set the maximum as "Inf" for infinite. Comments can be used as a section to describe special Substances. As of now, the information here will only be reflected to the Spec Sheet.

Ex: "%SUBSTANCE:Substrate, 1, 10" means that the amount of the substrate is between 1 and 10.

@NOTES line is to define any comments that need to be noted.

### Reactor Source Code Keywords

• %PARAMETER:
• %INCLUDE_FILE_H:
• @PRIVATE:
• @PROTECTED:
• @PUBLIC:
• %INCLUDE_FILE_C:
• @INITIALIZE_FUNC:
• @REACT_FUNC:
• @OPTION_C:

%PARAMETER line is to define the parameters that become the argument for that Reactor in parameter name, type, unit, comment format separated by commas ",". Input "Int" or "Float" as parameter type according to the value (which are NOT identical to the "int"s and "float"s used for C++). "Int"s in E-CELL2 Windows version are 32bit integers and "Float"s are 80bit firm decimals (but because of JNI(Java Native Interface), the accuracy is 64 bit in the GUI version and 80bit in the batch version)
%INCLUDE_FILE_H line is to define the .h filename to be included in the reactor. Do not embrace file names with < > or " ".
@PRIVATE line is to define private items used. @PROTECTED line is to define restricted items used.
@PUBLIC line is to define the public items used.

If FluxReactor.h is included in the file, Reactor.h, Reactant.h, and RootSystem.h are all automatically included in the file are need not to be included. Note that Stepper.h used in E-CELL1 is not used in E-CELL2. If not including FluxReactor.h, including StandardHeaders.h is desired in ordered to include the former three header files.

@OPTION_C line is to define new methods and macros. The data here will be appended to the top of the .cpp file.

@INITIALIZE_FUNC line is to define the C++ code to be executed only once at the initialization point. This line can be used to set the non-changing elements and to check parameter ranges.

@REACT_FUNC line is to define the process that must be done for each calculation step. As default:

1. Calculate Reaction Velocity
2. Alter the substance value according to the Velocity

if including the FluxReactor, process() method can be used to easily perform the 2. task. Argument for the process() method is the molecular reacting amount per second(in Float).

The activity that the reactor handle is the value per single step, but the value shown in the reactor window are values per second.

 KEYWORD .tex .cpp .h format required @CLASSNAME O O O . O @BASECLASS O O O . O @AUTHOR O (*1) (*1) . . @EMAIL O (*1) (*1) . . @DATE O (*1) (*1) . . %VERSION O O O . . @BRIEF_DESCRIPTION O . O . . @DESCRIPTION O . . TEX . @EQUAION O . . TEX . %SUBSTANCE O . . . O(*2) %PARAMETER O O O . O(*2) @NOTES O . . TEX . %INCLUDE_FILE_H . . O . . @PRIVATE . . O C++ . @PROTECTED . . O C++ . @PUBLIC . . O C++ . %INCLUDE_FILE_C . O . . . @INITIALIZE_FUNC . O . C++ O @REACT_FUNC . O . C++ O @OPTION_FUNC . O . C++ .

Figure: Keywords (target file, format)
 (*1) will be treated as comments (*2)Dependent on the Reactor

 Method Definition N_A Avogadro amount deltaT() Step range (E-CELL1: supersystem()->stepper()->deltaT ) numSubstrate() Substrate amount numProduct() Product amount numCatalyst() Catalyst amount numEffector() Effector amount substrate(i)->coefficient() ith Substrate stoichiometry substrate(i)->concentration() ith Substrate concentration in M substrate(i)->quantity() ith Substrate molecular amount substrate(i)->substance().supersystem()->volume() System Volume of the ith Substrate product(i)->coefficient() ith Product stoichiometry product(i)->concentration() ith Product concentration in M product(i)->quantity() ith Product molecular amount product(i)->substance().supersystem()->volume() System Volume of the ith Product catalyst(i)->concentration() ith Catalyst concentration in M catalyst(i)->quantity() ith Catalyst molecular amount catalyst(i)->substance().supersystem()->volume() System Volume of the ith Catalyst effector(i)->concentration() ith Effector Concentration in M effector(i)->quantity() ith Effector molecular amount effector(i)->substance().supersystem()->volume() System Volume of the ith Effector

Figure: Method list

## 2.2 Reactor Description Example

In order to create a Reactor file for the kinetic equation such as one below:

v = (KcFKp[S] - KcRKs[P])[E]
Ks[P] + Kp[S] + KsKp

we shall name the Reaction "MichaelisUniUniReversibleReactor" and the keyword definition will be such as the following:

@CLASSNAME:MichaelisUniUniReversibleReactor

@BASECLASS: FluxReactor
@AUTHOR: Kouichi Takahashi
@EMAIL: shafi@sfc.keio.ac.jp
@DATE: 1999 2/22

%VERSION: ecs-v08, 0.1

@BRIEF_DESCRIPTION:Simple Henri-Michaelis-Menten UniUni Reversible kinetics.
@DESCRIPTION:Simple Henri-Michaelis-Menten UniUni Reversible kinetics.
@EQUATION:$$v=\frac{(K_{cF} K_p [S]-K_{cR} K_s[P])[E]}{K_s[P]+K_p[S]+Ks Kp}$$

%SUBSTANCE:Substrate, 1, 1
%SUBSTANCE:Product, 1, 1
%SUBSTANCE:Catalyst, 1, 1
%SUBSTANCE:Effector, 0, 0

%PARAMETER: Ks, Float, mol/l, Michaelis Constant of Substrate
%PARAMETER: Kp, Float, mol/l,Michaelis Constant of Product
%PARAMETER: KcF, Float, mol/l, Catalytic Constant (Forward)
%PARAMETER: KcR, Float, mol/l,Catalytic Constant (Reverse)

@PRIVATE: Float Ksp;

@INITIALIZE_FUNC:
Ksp = Ks * Kp;
@REACT_FUNC:
Float S = substrate(0)->concentration();
Float P = product(0)->concentration();
Float E = catalyst(0)->quantity();

Float velocity = (KcF * Kp * S - KcR * Ks * P) * E / (Ks * P + Kp * S + Ksp);

process(velocity);


For Ks and Kp are both parameters in the equation, The product (Ks * Kp) will always be constant. Thus, the product of this function need only be calculated once at the initialization point. Declaring Ksp as a @PRIVATE function:

@INITIALIZE_FUNC
Ksp = Ks * Kp;

In the @REACT_FUNC line, variable S must be declared to describe Substrate concentration. Thus:

@REACT_FUNC Float S=Substrate(0)->concentration();

P and E must identically be declared.

# 3 Conversion to Reactor Source Code (.C .h file) and DLL

To create Reactor source and executable (DLL) modules for E-CELL2 system, first press the Reactor tab of the ModelingLauncher. By selecting the .rd for input and pressing the "Execute" button, the launcher will automatically create the source code and DLL files by compiling. Refer to the ModelingLauncher tutorial in Chapter 6 for more details.

Figure: Modeling Launcher

# 4 Load the E-CELL2 System

In order for E-CELL2 to be executed, the following precautions must be noted. The Reactor (dll files) defined in the Rule must be placed under the Reactor Directory (As default, DLLR and DLLRB are set in ECELL2.BAT and ECELL2BB.BAT). Normally the created reactor dlls will be placed in these directories. E-CELL2 will terminate with an error message if the designated Reactor itself or the path do not exist.

# 5 General Reactors from the E-CELL2 Project

 Reactor Classname Reversible/Irreversible Reaction ZeroReactor I zero order reaction MassActionReactor I 1st order reaction MichaelisUniUniReactor I follow MichaelisMenten MichaelisUniUniReversibleReactor R follow MichaelisMenten RapidEquilibriumReactor R rapid equilibrium ConstantParameterReactor I Constant OrderedUniBiReactor R . OrderedBiUniReactor R . OrderedBiBiReactor R . PingPongBiReactor I . PingPongBiBiReactor R . RandomUniBiReactor R . RandomBiUniReactor R . RandomBiBiReactor R . RapidEquilibriumReactor R . IsoUniUniReactor R . CatalyzedMassActionReactor R . DecayReactor I . GeneralRapidEquilibriumPReactor - . RapidEquilibriumPReactor - .

Figure: Standard Reactor

Acrobat Reactor is required to view a pdf file.

 E-CELL2 User's Manual Last Update $Date: 2003/3/25$. Copyright: Keio University and Mitsui Knowledge Industry Co., Ltd. 2000-2003 Chapter 5: Creating User Defined Reactor Files [Chapter 1:Chapter 2:Chapter 3:Chapter 4:Chapter 6][Top]