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Modelling (Minor 1)
Modelling (Minor 1)
OPTIMIZATION OF BIOPROCESSES
BT401
Dr.R.Satish Babu
CONTENTS
• Introduction
• Modelling Principles & Fundamentals of
Modelling
• Modeling approaches
• Neural network modeling
• Simulation using Berkely Madonna Program
• Optimization
What is “Model”
Model
• Three-dimensional representation of a person
or thing or of a proposed structure, typically
on a smaller scale than the original
• synonyms:replicareplica, copyreplica, copy, re
presentationreplica, copy, representation, mo
ck-upreplica, copy, representation, mock-up, d
ummyreplica, copy, representation, mock-up,
dummy, imitationreplica, copy, representation
, mock-up, dummy, imitation, doublereplica, c
opy, representation, mock-up, dummy, imitati
Model?
• A thing used as an example to follow or
imitate
• synonyms:prototypeprototype, stereotypepro
totype, stereotype, archetype,
• versionversion, style.
What is a Scientific Model?
• A scientific model is a representation of a
particular phenomenon in the world using
something else to represent it, making it
easier to understand
• A scientific model could be a diagram or
picture, a physical model like an aircraft
model, a computer program, or set of complex
mathematics that describes a situation.
Model?
• Graphical / Physical (Visual Models),
mathematical (symbolic)representation or
simplified version of a concept
• Visual models are things like flowcharts,
pictures, and diagrams that help us educate
each other
Use?
• The goal is to make the particular thing you're
modeling easier to understand.
• When we do that, we're able to use it to
predict what will happen in the future.
• For example, predicting what will happen as
our climate changes would be easy if we could
make a fully accurate model of the
atmosphere.
• A representation of a system that allows for
investigation of the properties of the system
and, in some cases, prediction of future.
• Scientific models are often mathematical
models, where you use math to describe a
particular phenomenon.
• For example, M-M model
Use of models in Bioprocess?
• Use of Models for Understanding, Design and
Optimization of Bioreactors
Use of models in Bioprocess?
Mechanistic models
Fig.3 Classification of models as mechanistic and nonmechanistic
Different perspectives for cell population kinetic representation (Adapted from
Bailley and Ollis,1986)
Integrative dynamic model
• Large population
• Single initial case
• Rest of the population is fully susceptible
Examples:
– Influenza pandemics
– SARS
– Ebola
– Covid-19
The equations
Parameters:
Assumptions:
▪ Homogeneous mixing
▪ Constant recovering rate
SIR output: the epidemic curve
S I R
Susceptible
Removed
Proportion of population
Infectious
Time
Full dynamics
Enzyme Kinetics - Inhibition
Types of Inhibition
• Competitive Inhibition
• Noncompetitive Inhibition
• Uncompetitive Inhibition
• Irreversible Inhibition
Competitive Inhibition
In competitive inhibition,
the inhibitor competes
with the substrate for the
same binding site
Competitive Inhibition
- Reaction Mechanism
Vmax,app = Vmax
Km,app > Km
The Lineweaver-Burk plot is
diagnostic for competitive inhibition
Relating the Michaelis-Menten equation, the v vs. [S]
plot, and the physical picture of competitive inhibition
Inhibitor
competes with
substrate,
decreasing its
apparent affinity:
Km,app > Km
Km,app > Km
Formation
FormationofofEI EI Vmax,app = Vmax
complex
complex shifts
shiftsreaction
reaction
to
to the
the left:
left:KKm,app >>KKm
m,app m
Example - Competitive Inhibition
Sulfanilamide is a competitive
inhibitor of p-aminobenzoic
acid. Sulfanilamides (also
known as sulfa drugs,
discovered in the 1930s)
were the first effective
systemic antibacterial
agents.
Because we do not make folic
acid, sulfanilamides do not
affect human cells.
Practical case: Methanol poisoning
the inhibitor
does not
interfere with
substrate
binding (and
vice versa)
Noncompetitive Inhibition -
Reaction Mechanism
In noncompetitive
inhibition, the
inhibitor binds
enzyme
irregardless of
whether the
substrate is bound
Noncompetitive inhibitors decrease the
Vmax,app, but don’t affect the Km
Even at high
substrate levels, Km,app > K< mVmax
Vmax,app
Formation inhibitor
of EI still binds, Vmax,app ==V
[E]t < reaction
[ES] K Kmax
complex shifts m,app m
Vmax,app < Vmax
to the left: Km,app > Km
Noncompetitive inhibitors
decrease the apparent Vmax, but
do not alter the Km of the
reaction
Example of noncompetitive inhibition:
fructose 1,6-bisphosphatase inhibition by AMP
Fructose 1,6-bisphosphatase is a key regulatory
enzyme in the gluconeogenesis pathway. High
amounts of AMP signal that ATP levels are low and
gluconeogenesis should be shut down while
glycolysis is turned on.
High AMP levels inhibit fructose 1,6-bisphosphatase
(shutting down gluconeogenesis) and activate
phosphofructokinase (turning on glycolysis).
Regulation of fructose 1,6-bisphosphatase and
phosphofructokinase by AMP prevents a futile cycle
in which glucose is simultaneously synthesized and
broken down.
Uncompetitive Inhibition
In uncompetitive
inhibition, the
inhibitor binds
only to the ES
complex
Uncompetitive Inhibition -
Reaction Mechanism
In uncompetitive
inhibition, the
inhibitor binds only
to the ES complex,
it does not bind to
the free enzyme
Uncompetitive inhibitors decrease
both the Vmax,app and the Km,app
Vmax,app < Vmax
Km,app < Km
Notice that at low substrate
concentrations,
uncompetitive inhibitors
have little effect on the
reaction rate because the
lower Km,app of the enzyme
offsets the decreased Vmax,app
Uncompetitive inhibitors decrease both the
Vmax,app and the Km,app of the enzyme
Notice that
uncompetitive inhibitors
don’t bind to the free
enzyme, so there is no
EI complex in the
reaction mechanism
The Lineweaver-Burk plot is
diagnostic for uncompetitive inhibition
Relating the Michaelis-Menten equation, the v vs. [S]
plot, and the physical picture of uncompetitive inhibition
Inhibitor
Vmax,app < Vmax
increases
the amount of Km,app< Km
enzyme bound
to substrate
Km,app < Km
Even at high
Formation of EI levels,
substrate
complex shiftsinhibitor binds,
reaction
[E]t < [ES]
to the left: KVm,app >< V
Km
max,app max
Uncompetitive inhibitors
decrease the apparent Km of the
enzyme and decrease the Vmax of
the reaction