“PROBABILITY AND STATISTICS”

“(ASSIGNMENT #2)”
TOPIC OF THE ASSIGNMENT
SIMPLE PROBABILITY, CONDITIONAL PROBABILITY, LAW
OF ADDITION, LAW OF MULTIPLICATION, INDEPENDENT
EVENTS
COURSE CODE: STAT-205
SUBMITTED TO: MADAM AMNA
SUBMITTED BY: GROUP NO.08

NAME ROLL NO.

MAHNOOR 19021560-025

LAIBA TANZEEM 19021560-027

MUQADDAS 19021560-035

HAMNA ANWAR 19021560-037

MUHAMMAD USAMA 19021560-043

CLASS AND SECTION: BS-IT 19TH BATCH (B)

DEPARTMENT: INFORMATION TECHNOLOGY

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 Drug Design:
What is a drug?
“A drug is a chemical substance used in treatment, cure, prevention or
diagnosis of disease or used to otherwise enhance physical or mental well-being.”
 Drug is most commonly an organic small molecule that activates/inhibits
function of bio-molecule such as protein which in turn results in therapeutic
benefit to the patient.
Drug design:
“It is the innovative process of finding new medications based on the
knowledge of a biological target.”
 It involves design of a small molecules that are complementary in shape and
charge to bio-molecular target.
 Based on study of structures and functions of target molecules.
 Drug design is to use a methodological approach to coming up with a new
drug
2 ways of drug designing:
 Development of ligands with desired properties for the targets having known
structure and function.
 Development of ligands with predefined properties for the targets whose
structural information may be or may not be known.
General steps to create a new drug:
It involves 3 steps:
 Identify a receptor/enzyme that is relevant to a disease they are going to
design a drug for.
 Elucidate the structure and function of this receptor/enzyme.
 Use the information from step 2 in order to design a drug molecule that
interacts with the receptor/enzyme in a therapeutically beneficial way.
Drug target:
 Target- molecular recognition site to which drug binds.

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 Drug target is a key molecule involved in particular metabolic/signaling
pathway that is specific to a disease condition or pathology or to the
infectivity or survival of a microbial pathogen.
 The target may be;
 Protein molecule
 A receptor
 Enzyme
 Transport molecule
 Ion channel
 Tubulin
 Immunophilin
History:
-PLANT/NATURAL PRODUCT
 Plant and natural products were source for medical substance.
 Example: foxglove used to treat congestive heart failure.
-ACCIDENTAL OBSERVATIONS
 1928: Alexander Fleming observed the effect of mold.
 Mold (Penicillium) produce substance penicillin.

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Techniques of drug design:
 X-ray crystallography:
 Starting point for gathering info from mechanistic drug design.
 Determine structural info about molecule.
 Provides critically important coordinates needed for handling of data by
computer modeling system.
 Nuclear magnetic resonance(NMR):
 Uses much softer radiation.
 Examine molecules in more mobile liquid phase.
 3-D info will be obtained.
 Examines small molecule-macro molecule complexes.
 Homology modeling:
 Also called as comparative modeling of protein.

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 Constructing an atomic-resolution model of “target” and an experimental 3-D
structure of related homologous protein.
 Computer aided drug design:

Steps involved in drug designing:

1. Target identification:
 Target is a molecule namely a protein which is present within an organism.
 Approaches of identifying targets include proteins expression, protein
biochemistry, structure function studies, study of biochemical pathways.
 Several other methods to identify specific molecular targets like HTSA,
positional cloning, generation of cdna libraries with ests and database mining
by sequence homology.
 Important to determine whether the novel targets are actually relevant to
physiology of the disease.
2. Target validation:
 As there are plethora of new potential therapeutic drug targets that are being
discovered, selection and validation of novel molecular targets has become
important.
 Needs to be confirmed that targets identified will affect an appropriate
biological response.
 Tgd is a term that refers to several different methods of target validation.

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3. Lead identification:
 lead is a compound that demonstrates desired biological activity on a
validated molecular target.
 To be termed as a lead, compound must exceed specific potency threshold
against target.
 Compounds used as potential leads can be from many sources e.g. peptide
libraries, natural compounds.
4. Lead optimization:
 Once a lead compound is established in identification process, we need to
optimize desirable traits of the lead.
 To be considered for further development, lead should be amenable for
chemistry optimization.
5. Docking:
 Refers to ability to position ligand in active/designated site of protein and
calculate specific binding affinities.
 Docking algorithms can be used to find ligands and binding conformations at a
receptor site close to experimentally determined structures.
 Used to identify multiple proteins to which small molecule can bind.
6. Pre- clinical trails:
 It is study of how drug molecule interacts with its molecular target.
 Pharmacological techniques employed to study receptor binding, functional
effect, dose responses etc.
 Ad -met characteristics are very important at this stage.
 Absorption; compounds are delivered by range of routes in the body.
 From site of initial delivery compounds will be absorbed in specific patterns.
 Distribution; once absorbed compounds is distributed throughout the body is
determined by a route of administration and formulation.
7. Clinical trails:
 Before a drug is approved, clinical trials have to be followed.
It has distinct phases:
 Phase 0-> micro dosing of candidate to determine distribution related info.
 Phase 1-> 1st stage testing in humans.
 Phase 2-> access how well the drug works.
 Phase 3-> multi center trials on large patients groups.
 Phase 4-> involves safety surveillance and ongoing technical support of a drug
after receiving permission to be sold.

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 Drugs designing and its types

There are two major types of drug design. The first is referred to as ligand-based drug design and
the second, structure-based drug design.

1. Ligand-based:
Ligand-based drug design (or indirect drug design) relies on knowledge of other molecules
that bind to the biological target of interest. These other molecules may be used to derive
a pharmacophore model that defines the minimum necessary structural characteristics a
molecule must possess in order to bind to the target. In other words, a model of the biological
target may be built based on the knowledge of what binds to it, and this model in turn may be
used to design new molecular entities that interact with the target. Alternatively, a quantitative
structure-activity relationship (QSAR), in which a correlation between calculated properties of
molecules and their experimentally determined biological activity, may be derived. These QSAR
relationships in turn may be used to predict the activity of new analogs.

2. Structure-based:
Structure-based drug design (or direct drug design) relies on knowledge of the three
dimensional structure of the biological target obtained through methods such as x-ray
crystallography or NMR spectroscopy. If an experimental structure of a target is not available,
it may be possible to create a homology model of the target based on the experimental structure
of a related protein. Using the structure of the biological target, candidate drugs that are
predicted to bind with high affinity and selectivity to the target may be designed using interactive
graphics and the intuition of a medicinal chemist. Alternatively various automated computational
procedures may be used to suggest new drug candidates.
Current methods for structure-based drug design can be divided roughly into three main
categories. The first method is identification of new ligands for a given receptor by searching
large databases of 3D structures of small molecules to find those fitting the binding pocket of
the receptor using fast approximate docking programs. This method is known as virtual
screening. A second category is de novo design of new ligands. In this method, ligand molecules
are built up within the constraints of the binding pocket by assembling small pieces in a stepwise
manner. These pieces can be either individual atoms or molecular fragments. The key advantage
of such a method is that novel structures, not contained in any database, can be suggested. A
third method is the optimization of known ligands by evaluating proposed analogs within the
binding cavity.
Binding site identification:
Binding site identification is the first step in structure based design. If the structure of the
target or a sufficiently similar homolog is determined in the presence of a bound ligand, then the
ligand should be observable in the structure in which case location of the binding site is trivial.

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 However, there may be unoccupied allosteric binding sites that may be of interest.
Furthermore, it may be that only apoprotein (protein without ligand) structures are available and
the reliable identification of unoccupied sites that have the potential to bind ligands with high
affinity is non-trivial. In brief, binding site identification usually relies on identification
of concave surfaces on the protein that can accommodate drug sized molecules that also possess
appropriate "hot spots" (hydrophobic surfaces, hydrogen bonding sites, etc.) that drive ligand
binding.
Scoring functions:
Structure-based drug design attempts to use the structure of proteins as a basis for
designing new ligands by applying the principles of molecular
recognition. Selective high affinity binding to the target is generally desirable since it leads to
more efficacious drugs with fewer side effects. Thus, one of the most important principles for
designing or obtaining potential new ligands is to predict the binding affinity of a certain ligand
to its target (and known anti-targets) and use the predicted affinity as a criterion for selection.
One early general-purposed empirical scoring function to describe the binding energy of
ligands to receptors was developed by Böhm. This empirical scoring function took the form:

A more general thermodynamic "master" equation is as follows:

where:
 desolvation – enthalpic penalty for removing the ligand from solvent
 motion – entropic penalty for reducing the degrees of freedom when a ligand binds to its
receptor
 configuration – conformational strain energy required to put the ligand in its "active"
conformation
 interaction – enthalpic gain for "resolvating" the ligand with its receptor

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 The basic idea is that the overall binding free energy can be decomposed into
independent components that are known to be important for the binding process. Each
component reflects a certain kind of free energy alteration during the binding process between
a ligand and its target receptor. The Master Equation is the linear combination of these
components. According to Gibbs free energy equation, the relation between dissociation
equilibrium constant, Kd, and the components of free energy was built.
Various computational methods are used to estimate each of the components of the
master equation. For example, the change in polar surface area upon ligand binding can be used
to estimate the desolvation energy. The number of rotatable bonds frozen upon ligand binding is
proportional to the motion term. The configurational or strain energy can be estimated
using molecular mechanics calculations. Finally the interaction energy can be estimated using
methods such as the change in non-polar surface, statistically derived potentials of mean force,
the number of hydrogen bonds formed, etc. In practice, the components of the master equation
are fit to experimental data using multiple linear regression. This can be done with a diverse
training set including many types of ligands and receptors to produce a less accurate but more
general "global" model or a more restricted set of ligands and receptors to produce a more
accurate but less general "local" model.

Rational drug discovery:

In contrast to traditional methods of drug discovery (known as forward pharmacology),
which rely on trial-and-error testing of chemical substances on cultured cells or animals, and
matching the apparent effects to treatments, rational drug design (also called reverse
pharmacology) begins with a hypothesis that modulation of a specific biological target may have
therapeutic value. In order for a biomolecule to be selected as a drug target, two essential pieces
of information are required. The first is evidence that modulation of the target will be disease
modifying. This knowledge may come from, for example, disease linkage studies that show an
association between mutations in the biological target and certain disease states. The second is
that the target is "druggable". This means that it is capable of binding to a small molecule and
that its activity can be modulated by the small molecule.
Once a suitable target has been identified, the target is
normally cloned and produced and purified. The purified protein is then used to establish
a screening assay. In addition, the three-dimensional structure of the target may be determined.
The search for small molecules that bind to the target is begun by screening libraries of
potential drug compounds. This may be done by using the screening assay (a "wet screen"). In
addition, if the structure of the target is available, a virtual screen may be performed of candidate
drugs. Ideally the candidate drug compounds should be "drug-like", that is they should possess
properties that are predicted to lead to oral bioavailability, adequate chemical and metabolic
stability, and minimal toxic effects. Several methods are available to estimate drug likeness such
as Lipinski's Rule of Five and a range of scoring methods such as lipophilic efficiency. Several
methods for predicting drug metabolism have also been proposed in the scientific literature.

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Due to the large number of drug properties that must be simultaneously optimized during the
design process, multi-objective optimization techniques are sometimes employed. Finally
because of the limitations in the current methods for prediction of activity, drug design is still
very much reliant on serendipity and bounded rationality.

Computer-aided drug design:

The most fundamental goal in drug design is to predict whether a given molecule will
bind to a target and if so how strongly. Molecular mechanics or molecular dynamics is most
often used to estimate the strength of the intermolecular interaction between the small
molecule and its biological target. These methods are also used to predict the conformation of the
small molecule and to model conformational changes in the target that may occur when the small
molecule binds to it. Semi-empirical, ab initio quantum chemistry methods, or density
functional theory are often used to provide optimized parameters for the molecular mechanics
calculations and also provide an estimate of the electronic properties (electrostatic
potential, polarizability, etc.) of the drug candidate that will influence binding affinity.
Molecular mechanics methods may also be used to provide semi-quantitative prediction
of the binding affinity. Also, knowledge-based scoring function may be used to provide binding
affinity estimates. These methods use linear regression, machine learning, neural nets or other
statistical techniques to derive predictive binding affinity equations by fitting experimental
affinities to computationally derived interaction energies between the small molecule and the
target.
Ideally, the computational method will be able to predict affinity before a compound is
synthesized and hence in theory only one compound needs to be synthesized, saving enormous
time and cost. The reality is that present computational methods are imperfect and provide, at
best, only qualitatively accurate estimates of affinity. In practice it still takes several iterations of
design, synthesis, and testing before an optimal drug is discovered. Computational methods have
accelerated discovery by reducing the number of iterations required and have often provided
novel structures.
Drug design with the help of computers may be used at any of the following stages of drug
discovery:
1. hit identification using virtual screening (structure- or ligand-based design)
2. Hit-to-lead optimization of affinity and selectivity (structure-based design, QSAR, etc.)
3. lead optimization of other pharmaceutical properties while maintaining affinity

Flowchart of a Usual Clustering Analysis for Structure-Based Drug Design:

In order to overcome the insufficient prediction of binding affinity calculated by recent
scoring functions, the protein-ligand interaction and compound 3D structure information are
used for analysis. For structure-based drug design, several post-screening analyses focusing on
protein-ligand interaction have been developed for improving enrichment and effectively mining
potential candidates:

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Consensus scoring:
 Selecting candidates by voting of multiple scoring functions
 May lose the relationship between protein-ligand structural information and scoring
criterion
Cluster analysis:
 Represent and cluster candidates according to protein-ligand 3D information
 Needs meaningful representation of protein-ligand interactions.

Enzyme as target for drugs design

“A drug target is a molecule in the body, usually a protein, that is intrinsically
associated with a particular disease process and that could be addressed by
a drug to produce a desired therapeutic effect”.
A drugs target interaction:
¥ Drugs are chemically synthesized chemicals that control, prevent, cure and
diagnose various diseases and illness.
¥ They do so by reacting with various macromolecules and elicit some of
positive biological response.
¥ The macromolecule (proteins, lipids) is called target which is responsible
for different function of our body.
¥ Action of drug depend upon the interaction between the drugs molecule
and the molecules that its target.
Biomolecules as target
There are many Biomolecules as target such as:

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 En zym
e
recp to rs r o
p tein s
rm o
o
H n es n
io
ch n
ea ls

When it’s come to drug target interaction enzyme and receptor are considered.

Why are enzymes important targets for drugs?

Enzymes catalyze multistep chemical reactions and achieve phenomenal rate
accelerations by matching protein and substrate chemical groups in the transition
state. Inhibitors that take advantage of these chemical interactions are among the
most potent and effective drugs known. The catalytic chemistry of enzymes is the
key to designing potent inhibitors and makes them a special class of drug target.
¥ Enzymes (especially protein kinases, proteases, esterases, and phosphatases)
are known as drug target.
¥ Many important drugs act as enzyme Inhibitors.
¥ They hinder or prevent enzyme acting as catalysts for a particular reaction.

Catalytic action of enzyme

1o In order to carry catalytic activity enzymes perform 2 major functions:

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 The first function of an enzyme is to hold the substrate for a chemical
reaction. Active sites of enzymes hold the substrate molecule in a suitable
position, so that it can be attacked by the reagent effectively.
 Substrates bind to the active site of the enzyme through a variety of
interactions such as ionic bonding, hydrogen bonding, van der Waals
interaction or dipole-dipole interaction.
 The second function of an enzyme is to provide functional groups that will
attack the substrate and carry out chemical reaction

Mechanistic view of substrate converts into the product

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 Drug-Enzyme Interaction
î These drugs can block the binding site of the enzyme and prevent the
binding of substrate, or can inhibit the catalytic activity of the enzyme. Such
drugs are called enzyme inhibitors.

î Drugs inhibit the attachment of substrate on active site of enzymes in two

different ways;

î Drugs compete with the natural substrate for their attachment on the active
sites of enzymes. Such drugs are called competitive inhibitors.

î Some drugs do not bind to the enzyme’s active site. These bind to a different
site of enzyme which is called allosteric site. This binding of inhibitor at
allosteric site changes the shape of the active site in such a way that
substrate cannot recognise it.

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 Allosteric inhibition example as enzyme as drug target
One example of an important drug that takes on the role of an allosteric inhibitor is
the antibiotic penicillin. By helping the body kill off harmful bacteria, penicillin
has saved millions of lives.

Harmful bacteria rely on the enzyme DD-transpeptidase to create strong,

mesh-like cell walls. To counteract this process, penicillin binds to this enzyme.
By acting as an inhibitor, penicillin prevents bacteria from building strong

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 cell walls. With a weak wall, the surrounding fluids of the bacteria cell can
then push itself in through osmosis. The cell will then burst and dies.
Allosteric inhibition is the slowing down of enzyme-catalyzed chemical
reactions that occur in cells. These metabolic processes are responsible for the
proper functioning and maintenance of our bodies’ equilibrium, and allosteric
inhibition can help regulate these processes.

 Competitive inhibition:
 Definition:
In competitive inhibition, an inhibitor that resembles the normal substrate binds to the enzyme,
usually at the active site, and prevents the substrate from binding.
At any given moment, the enzyme may be bound to the inhibitor, the substrate, or neither, but it
cannot bind both at the same time.

OR
In competitive inhibition of enzyme catalysis, binding of an inhibitor prevents binding of the
target molecule of the enzyme, also known as the substrate. This is accomplished by blocking the
binding site of the substrate the active site by some means.

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 Competitive inhibition can be overcome by adding more substrate to the reaction, which
increases the chances of the enzyme and substrate binding. 

 Mechanism:
In competitive inhibition, an inhibitor that resembles the normal substrate binds to the enzyme,
usually at the active site, and prevents the substrate from binding.
During competitive inhibition, the inhibitor and substrate compete for the active site.
“The active site is a region on an enzyme to which a particular protein or substrate can bind”.
The active site will thus only allow one of the two complexes to bind to the site, either allowing a
reaction to occur or yielding it. In competitive inhibition, the inhibitor resembles the substrate,
taking its place and binding to the active site of an enzyme. Increasing the substrate
concentration would diminish the "competition" for the substrate to properly bind to the active
site and allow a reaction to occur. When the substrate is of higher concentration than the
concentration of the competitive inhibitor, it is more probable that the substrate will come into
contact with the enzyme's active site than with the inhibitor.

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  Role of Competitive inhibitors in pharmaceuticals:
Competitive inhibitors are commonly used to make pharmaceuticals.
 For example, 
Methotrexate is a chemotherapy drug that acts as a competitive inhibitor. It is structurally
similar to the coenzyme, foliate , which binds to the enzyme DHFR. This enzyme is part of the
synthesis of DNA and RNA, and when methotrexate binds the enzyme, it renders it inactive, so
that it cannot synthesize DNA and RNA. The cancer cells are thus unable to grow and divide.
Another example:
 Prostaglandin made in large amounts as a response to pain and can cause inflammation.
Essential fatty acids form the prostaglandins; when this was discovered, it turned out that these
were actually very good inhibitors to prostaglandins.
‘These fatty acids inhibitors have been used as drugs to relieve pain because they can act as the
substrate, and bind to the enzyme, and block prostaglandins’.

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Competitive inhibition can be reversible or irreversible.
 If it is reversible inhibition, then effects of the inhibitor can be overcome by increasing
substrate concentration.
 If it is irreversible, the only way to overcome it is to produce more of the target (and
typically degrade or excrete the irreversibly inhibited target).

 Effect of Competitive inhibition on Rate of Reaction:

In competitive inhibition, the maximum velocityV max of the reaction is Unchanged, while the
apparent affinity of the substrate to the binding site is decreased (the K d  dissociation constant is
apparently increased).
The change in  K m which is called constant Michaelis Menten is parallel to the alteration  K d , as
one increases the other must decrease.
When a competitive inhibitor is bound to an enzyme the K mincreases. This means the binding
affinity for the enzyme is decreased, but it can be overcome by increasing the concentration of
the substrate. Any given competitive inhibitor concentration can be overcome by increasing the
substrate concentration.
In that case, the substrate will reduce the availability for an inhibitor to bind, and, thus, outcome
the binding of inhibitor in binding to the enzyme.

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 Biological examples:
Sulfa drugs also act as competitive inhibitors.
For example: 
1. Sulfanilamide competitively binds to the enzyme in the Dihydropteroate
Synthase (DHPS) active site by mimicking the substrate Para Aminobenzoic
acid (PABA).

This prevents the substrate itself from binding which halts the production of folic acid, an
essential nutrient. Bacteria must synthesize folic acid because they do not have a transporter for
it. Without folic acid, bacteria cannot grow and divide.
Therefore, because of sulfa drugs' competitive inhibition, they are excellent antibacterial agents.
2. An example of competitive inhibition was demonstrated experimentally for the enzyme
succinic dehydrogenase, which catalyzes the oxidation of succinate to Fumarate in the Krebs
cycle. 
Malonate is a competitive inhibitor of succinic dehydrogenase. The binding of succinic
dehydrogenase to the substrate, succinate, is competitively inhibited. This happens because
malonate's chemistry is similar to succinate. Malonate's ability to inhibit binding of the enzyme

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and substrate is based on the ratio of malonate to succinate. Malonate binds to the active site of
succinic dehydrogenase so that succinate cannot. Thus, it inhibits the reaction.

Non-Competitive inhibition 

Definition:
a type of enzyme inhibition where the inhibitor reduces the activity of the enzyme and binds
equally well to the enzyme whether or not it has already bound the substrate.

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  The inhibitor usually binds to a different domain on the enzyme, other than the
substrate binding site.
 This occurs when the substances not resembling the geometry of the substrate & do
not exhibit mutual competition. Since these inhibitors have no structural resemblance
to the substrate, an increase in the substrate concentration generally does not relieve
this inhibition.
 Strong affinity for inhibitors
 Prevent catalysis possibly due to distortion in enzyme conformation
 A variety of poisons, such as iodoacetate, heavy metal ions (lead, mercury) and
oxidizing agents act as irreversible non-competitive inhibitors. 
Types:
There are two types of Noncompetitive inhibition

i. If the inhibitor can be removed from its site of binding without affecting the activity
of the enzyme, it is called as Reversible-Non-competitive Inhibition.

ii. If the inhibitor can be removed only at the loss of enzymatic activity, it is known as
Irreversible Non-competitive Inhibition.

Examples for Non- Competitive Inhibition:

1. Enzymes requiring divalent metal ions (e.g., Mg2+ & Ca2+ etc.) for their activity are
inhibited non-competitively by chelating agents like EDTA which removes metal ions
from the enzyme.
2. Enzymes with -SH groups that participate in the maintenance of the three-
dimensional conformation of the molecule are non-competitively inhibited by heavy
metal ions. 

Characteristics of Noncompetitive Inhibition:

1. Reversible but not reversed by substrate.
2. Inhibitor binds at site other than substrate binding site
3. It binds reversibly to both free enzyme & ES complex to form inactive complex EI &
ESI.

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 E + I ↔ EI
ES + I ↔ ESI

4. Inhibitors alter the conformation of E

molecule so that reversible activation occurs.
5. They are naturally occurring metabolic
intermediates.
6. Most probably the sites of attachment of the
substrate and inhibitor are different.
7. This probably brings about the changes in 3D
structure of the enzyme inactivating it
catalytically.
Mechanism:
1. The inhibitor binds at an allosteric site separate from the active site of substrate
binding.
2. Binding of the inhibitor to the enzyme or enzyme-substrate complex inactivates the
enzyme, disallowing the production of its end product.
3. Inactivation of the enzyme decreases Vmax and Km remains unchanged.

Effect on Vmax:
 Noncompetitive inhibition cannot be overcome by increasing the concentration of
substrate.
 Therefore, noncompetitive inhibitors decrease the apparent Vmax of the reaction.
Effect on Km:
 Noncompetitive inhibitors do not interfere with the binding of substrate to enzyme.
 Therefore , the enzyme shows the same Km in the presence or absence of the
noncompetitive inhibitor.
Effect on Lineweaver-Burk plot:
Noncompetitive inhibition is readily differentiated from competitive inhibition by plotting
1/vo versus 1/[S] and noting that the apparent Vmax decreases in the presence of a
noncompetitive inhibitor, whereas Km is unchanged.
Note: Oxypurinol, a metabolite of the drug allopurinol, is a noncompetitive inhibitor of
xanthine oxidase, an enzyme of purine degradation.

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Clinical importance of non-competitive inhibition:
Cyanide inhibits cytochrome oxidase.
Fluoride will remove magnesium and manganese ions and so will inhibit the enzyme,
enolase, a consequently the glycolysis.
Iodoacetate would inhibit enzymes (Glyceraldehyde-3-P dehydrogenase, papain) having –
SH group in their active centers.
BAL (British Anti-Lewisite; Dimercaprol) is used as an antidote for heavy metal
poisoning. The heavy metals act as enzyme poisons by reacting with the SH group. BAL has
several SH groups with which the heavy metal ions can react and thereby their poisonous
effects are reduced.
Di isopropyl fluorophosphates (DFP): Acetylcholinesterase enzyme cleaves acetylcholine
to form acetate and choline and therefore terminates the action of acetylcholine. Certain
chemicals e.g., Di isopropyl fluorophosphates (DFP) binds to the active site, serine of
acetylcholinesterase. As a result, acetylcholine accumulates and over-stimulates autonomous
nervous system including heart, blood vessels and glands. This leads to vomiting, salivation,
sweating, and in worst cases even death. DFP forms an irreversible covalent bond with
acetylcholinesterase, and activity can be regained only if new enzyme is synthesized.
Disulfiram (Antabuse): Used in treatment of alcoholism, the drug irreversibly inhibits the
enzyme aldehyde dehydrogenase preventing further oxidation of acetaldehyde which
accumulates and produces sickening effect leading to aversion to alcohol.

--------------------------------------------------Thank You----------------------------------------------------------------

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