Introduction to Chemical Kinetics and Computational Modeling

Hana El-Samad Byers Hall (QB3), Rm 403D

Why mathematics in biology?

input

A B C

A DE
B E F
A F B
output
Given some initial concentrations, what is output give some prescribed input?

Chemical reactions are collisions of molecules

Molecule A

Molecule B

A B C

A
Reactant A

Molecule A

time

A1

Change in Concentration: DA= A2-A1

Reactant A

A2

t1

t2

time
Change in time: Dt=t2-t1 Average rate of change in concentration during time Dt=

DA Dt

A1

Change in Concentration: DA= A2-A1

Reactant A

A2

t1 t2

Derivative of A with Respect to time

instantaneous rate of change in concentration during time dt=

dA dt

A
dA . A dt
Rate of change of A Degradation constant

Concentration of A

D A
dA k .D . A dt
Rate of change of A Concentration of D Production constant Degradation constant Concentration of A

A B C
dA k . A.B dt

nA mB C
dA n m k . A .B dt

D Ak 2 A B C C A B
dA k1.D . A k2 . A.B k2C dt
k2

k1

Reaching steady-state (equilibrium) k

D A
dA k .D . A dt

Steady-state: No more change in A

dA 0 dt
Production of A balances degradation A is constant

k.D . A 0
A K .D

Chemical Reactions inside the cell

Central Dogma of Molecular Biology

Transcription
Transcription factor

start
gene

DNA

end

promoter

terminator

mRNA Translation

Proteins

mRNA

ribosomes

Modeling activator binding and production of mRNA

start
gene promoter

end

terminator

A DNA A : DNA A : DNA mRNA A : DNA

k2

Fast slow

A DNA A : DNA

Fast

d [ A : DNA] k1. A.DNA k2 .[ A : DNA] 0 dt

k1. A.DNA k2 .[ A : DNA]
but

k1. A.DNA [ A : DNA] k2

DNAtotal

k1. A.DNA (1 k1. A ) DNA DNA [ A : DNA] DNA k2 k2

DNAtotal DNA k1. A (1 ) k2

DNAtotal DNA k1. A (1 ) k2

k1. A.DNA [ A : DNA] k2

k1 A k2 [ A : DNA] DNAtotal k1 1 A k2
k2 kd k1
Dissociation constant

Hill Function

A kd [ A : DNA] DNAtotal A 1 kd

[ A : DNA]

DNAtotal

A : DNA mRNA A : DNA

dmRNA k3 .[ A : DNA] 1mRNA dt
A kd [ A : DNA] DNAtotal A 1 kd

k2

A kd dmRNA k3 . DNAtotal 1mRNA A dt 1 kd

Cooperativity

start
gene

end

promoter

terminator

A 3 ( ) kd dmRNA k3 . DNAtotal 1mRNA A 3 dt 1 ( ) kd

Cooperativity

n molecules

start
gene

end

promoter

terminator

A n ( ) kd dmRNA k3 . DNAtotal 1mRNA A n dt 1 ( ) kd

Repressor

start
gene promoter

end

terminator

dmRNA 1 k3 . DNAtotal 1mRNA X n dt 1 ( ) kd

1 k3 . DNAtotal X n 1 ( ) kd