Transcript Avrama Blackwell George Mason University

Modelling Biochemical
Reactions - Tutorial
Second Latin American School
on Computational Neuroscience
Kim “Avrama” Blackwell
George Mason University
Three Types of Objects
•
Pools of molecules
–
•
Uni- and Bi-molecular Reactions
–
•
Keep track of concentration
Transformation of one or more molecules into
equal number of another molecule
Enzyme reactions
–
One enzyme molecule can transform multiple
copies of substrate into equal number of product
Compartment-Like Objects
•Keep track of molecule quantities and
concentrations
•
Similar to compartment calculating voltage
–Requires
geometry/morphology values
•
length
•
radius
•
area of outer surface
•
area of inner surface (can be zero)
•
area of side surface
•
volume
Compartment-Like Objects
•
Keep track of molecule quantities and
concentrations
–
rxnpool (Chemesis)
•
dC/dt =  A -  B C
•
A = change in quantity independent of present
quantity
•
B = rate of change
•
Receives messages with quantities A and/or B from
other objects (enzymes, reactions, also calcium influx)
•RXN0
(A), RXN1 (B), RXN2 (A and B)
Compartment-Like Objects
•
Keep track of molecule quantities and
concentrations
–
–
conservepool (Chemesis)
•
C = Ctot - Ci
•
Quantity is remainder after all other forms of molecule
accounted for
pool (Kinetikit)
•
dC/dt =  A -  B C
•
Or C = Ctot - Ci
•
Can also implement stochastic reactions
(if flag is set to conserve)
Concentration Pools
•
chemesis
•
genesis #1 > showobject rxnpool
•
genesis #2 > showobject conservepool
•
genesis #3 > showobject pool
Enzyme and Reaction objects
•
Calculate changes due to reactions
–
mmenz (Chemesis)
•
Use if MM assumptions are met
•
Fields: Km and Vmax
•
Inputs: enzyme, substrate concentration
•
Calculates Vmax times [Enzyme] times [substrate]
divided by ([substrate] + Km)
•
Send messages RXN0 or RXN0moles to rxnpool
•
Empirical feedback modification of enzyme activity
can be added
Enzyme and Reaction objects
•
Calculate changes due to reactions
–
–
Enzyme (Chemesis)
•
Fields: Kcat, Kf, Kb
•
Inputs: enzyme, substrate quantity
•
Calculates amount of Enzyme-Substrate complex
•
Calculates change in product, enzyme, substrate
Enz (kinetikit)
•
Fields: Kcat, Kf, Kb
•
Inputs: enzyme, substrate quantity
•
Can implement stochastic reactions
Enzyme and Reaction objects
•
Calculate changes due to reactions
–
reaction (Chemesis) or reac (kinetikit)
•
Fields: kf, kb
•
Inputs (messages): substrates and products
•
Calculates:
•
–
forward rate constant times substrate molecules
–
backward rate constant times product molecules
send messages RXN0 - RXN2 to rxnpool
Enzyme and Reaction objects
•
Genesis #4> showobject mmenz
•
Genesis #5> showobject enzyme
–
Compartment dimensions allows membrane
bound enzyme to have different volume than
substrate and products
•
Genesis #5> showobject enz
•
Genesis #6> showobject reaction
•
Genesis #7> showobject reac
Creating Chemesis Simulation
•
Create rxnpool pool1
•
Create conservepool pool2
•
Setfield pool1 Cinit initvalue ...
•
Addmsg pool1 pool2 CONC Conc
–
mGlu-IP3-enz.g for complete examples
Creating Chemesis Simulation
•
•
•
•
•
•
Create reaction rxn1
Setfield rxn1 kf kfvalue kb kbvalue
Addmsg pool1 rxn1 SUBSTRATE Conc
Addmsg pool2 rxn1 SUBSTRATE Conc
Addmsg pool3 rxn1 PRODUCT Conc
Addmsg rxn1 pool1 RXN2 kbprod kfsubs
–
•
To substrate – kbprod is first
Addmsg rxn1 pool3 RXN2 kfsubs kbprod
–
To product – kfsubs is first
Chemesis Example
•
Metabotropic receptor to PLC to IP3
–
Include param.g
–
Include mGlu-IP3-enz.g
Listglobals
–
–
–
Create neutral purkcell
Create neutral glutamate (under purkcell)
•
Allow setting a concentration of neurotransmitter
–
Invoke function (no parentheses or commas)
Include graphs.g (and invoke function)
–
Step (to run simulation)
–
XPP example
•
Xppaut mglu-ip3.ode
–
Evaluate role of aG decay
–
Evaluate role of IP3 decay