Unit5 - Chandana Majee - Happi-1

Noida Institute of Engineering and Technology
(Pharmacy Institute) Greater Noida
UNIT V
INTRODUCTION TO DRUG DESIGN
Unit: V
Medicinal Chemistry III

Mrs.Chandana Majee
BP 601T
Asso. Prof.
B.Pharm NIET (Pharmacy
6th Sem Institute)
chandana majee BP 601T UNIT V

Reference:-https://www.slides 1
hare.net/SharadPatange2/qsar
Syllabus of Unit 5
Introduction to Drug Design
• Various approaches used in drug design.
• Physicochemical parameters used in quantitative structure
activity relationship (QSAR) such as partition coefficient,
Hammet’s electronic parameter, Tafts steric parameter and
Hansch analysis.
• Pharmacophore modeling and docking techniques.
Combinatorial Chemistry: Concept and applications
chemistry: solid phase and solution phase synthesis
Reference:-https://www.slides
chandana majee BP 601T UNIT V 2
Content
• Introduction of QSAR,
• Physicochemical parameters used for QSAR study
• Introduction of molecular docking
• Type of docking techniques
• Stages of docking
• Introduction of combinatorial chemistry
• Advantages combinatorial chemistry
• Principle of combinatorial chemistry
• Type of combinatorial chemistry
• Types of combinatorial techniques
Content
• Introduction of pharmacophore mapping
• Type (solid phase and solution phase technique)
• Application of pharmacophore mapping
• Video link and topic related online lecture
• Summary
• Daily quiz
• Weekly Assignment
• MCQs
• Old AKTU question paper
• Expected Questions for university Exam
• References
Course Objective
Upon completion of the course student shall be able to

1. Understand the importance of drug design and different
techniques of drug design.
2. Understand the chemistry of drugs with respect to their
biological activity.
3. Know the metabolism, adverse effects and therapeutic value of
drugs.
4. Know the importance of SAR of drugs.
Reference:-https://www.slides chandana majee BP 601T UNIT V

5
Course Outcome
After Completion of Course Students May be Able to
CO5
• Describe and compare various approaches used in drug design
such as QSAR, molecular docking , pharmacophore modeling
and combinatorial chemistry with their principle, advantages
and disadvantages
Course Outcome with blooms level of
taxonomy
CO No. CO STATEMENT LEVEL OF

TAXONOMY
CO5 Describe and compare Level II
various approaches used in (Understanding)
drug design such as QSAR,
molecular docking ,
pharmacophore modeling
and combinatorial chemistry
with their principle,
advantages and
disadvantages
Programme Outcomes (POs)
POs POs
No.
PO1 Pharmacy Knowledge: Possess knowledge and
comprehension of the core and basic knowledge associated
with the profession of pharmacy, including biomedical
sciences; pharmaceutical sciences; behavioral, social, and
administrative pharmacy sciences; and manufacturing
practices.
PO2 Planning Abilities: Demonstrate effective planning abilities

including time management, resource management,
delegation skills and organizational skills. Develop and
implement plans and organize work to meet deadlines
8
hare.net/SharadPatange2/qsar chandana majee BP 601T UNIT V
POs POs
No.
PO3 Problem analysis: Utilize the principles of scientific enquiry,
thinking analytically, clearly and critically, while solving
problems and making decisions during daily practice. Find,
analyze, evaluate and apply information systematically and
shall make defensible decisions.
PO4 Modern tool usage: Learn, select, and apply appropriate
methods and procedures, resources, and modern pharmacy-
related computing tools with an understanding of the
limitations.
9
POs POs
No.
PO5 Leadership skills: Understand and consider the human
reaction to change, motivation issues, leadership and team-
building when planning changes required for fulfillment of
practice, professional and societal responsibilities. Assume
participatory roles as responsible citizens or leadership roles
when appropriate to facilitate improvement in health and
wellbeing.
PO6 Professional Identity: Understand, analyze and

communicate the value of their professional roles in society
(e.g. health care professionals, promoters of health,
educators, managers, employers, employees).
POs Pos
No.
PO 7 Pharmaceutical Ethics: Honour personal values and apply
ethical principles in professional and social contexts.
Demonstrate behavior that recognizes cultural and personal
variability in values, communication and lifestyles. Use
ethical frameworks; apply ethical principles while making
decisions and take responsibility for the outcomes associated
with the decisions.
PO8 Communication: Communicate effectively with the
pharmacy community and with society at large, such as,
being able to comprehend and write effective reports, make
effective presentations and documentation, and give and
receive clear instructions.
Reference:-https://www.slides chandana majee BP 601T UNIT V 11
POs POs
No.
PO9 The Pharmacist and society: Apply reasoning informed by
the contextual knowledge to assess societal, health, safety and
legal issues and the consequent responsibilities relevant to the
professional pharmacy practice
PO Environment and sustainability: Understand the impact of

10 the professional pharmacy solutions in societal and
environmental contexts, and demonstrate the knowledge of,
and need for sustainable development

POs POs
No.
PO Life-long learning: Recognize the need for, and have the
11 preparation and ability to engage in independent and life-
long learning in the broadest context of technological
change. Self access and use feedback effectively from others
to identify learning needs and to satisfy these needs on an
ongoing basis.
13
CO-PO Mapping
Mapping of Course Outcomes with POs

The notation of 3, 2 and 1 denotes substantially (high),
moderately (medium) and slightly (low).
PO PO PO PO PO PO PO PO PO PO PO PO
1 2 3 4 5 6 7 8 9 10 11
CO5 3 - 2 3 - 1 - - 1 1 -
Prerequisite and Recap
Subject covers description of various new techniques used

for new drug discovery and identification along with their
uses. Student must have the knowledge of chemistry of drugs
and also about conceptof computer aided drug design (CADD)
Molecular Modeling(CO5)
 Molecular modeling is define as Theoretical methods and

computational techniques use to mimic the behavior of
molecules and molecular system.
 Molecular modeling helps the scientist to visualize molecule,
to discover new compounds for drugs.
 Vizualizing simple molecule in 3-Dimension to perform
complex
• computer simulations on large protein molecules.
• Goal :To develop a sufficient accurate model of the system so
that physical experiment is not necessary.
Reference:-https://www.slideshare.net/SharadPatange2/qsar-parameter
• Direct Drug Designing

 In this approach, the three dimensional features of
the known receptor site are determined from X-ray
crystallography to design lead molecule.
 Here, receptor site geometry is known; the
problem is to find a molecule that satisfies some
geometry constraints is also good chemical match.
 After finding good candidates according to
these criteria a docking step with energy
minimization can be used to predict binding strength.
• Indirect Drug designing

 Indirect drug design relies on knowledge of other
molecule that bind to the biological target of interst.
 These other molecules may be used to derive a
pharmacophore model that defines the minimum
necessary structural characteristics a molecule must
posses in order to bind to the target.
 The site geometry is not known,as is often the case,
the designer must base the design on other ligand
molecules that bind well to the site of receptor.
QSAR(CO5)
a.Molecular Mechanics (MM).

b.Quantum mechanics (QM).
Both these methods produce equations for the total energy (E) of the structure.
Molecular Modeling (CO5)
• Molecular Mechanics
 The Process of finding the minimum of an empirical potential
energy function is called as the Molecular mechanics. (MM)
 The process produce a molecule of idealized geometry.
 Molecular mechanics is a mathematical formalism
which attempts to reproduce molecular geometries, energies
and other features by adjusting bond lengths, bond angles and
torsion angles to equilibrium values that are dependent on the
hybridization of an atom and its bonding scheme.
 Molecular mechanics breaks down pair wise interaction

into
i) Bonded interaction ( internal coordination ).
-Atoms that are connected via one to three bonds ii).
Non bonded interaction .
-Electrostatic and Van der waals component
 The molecular mechanics energy expression consists of a

simple algebraic equation for the energy of the compound.
 A set of the equations with their associated constants which
are the energy expression is called a force field.
 Such equations describes the various aspects of the
equation like stretching, bending, torsions, electronic
interactions van der waals forces and hydrogen bonding.
 Some popular force fields are
 AMBER
 CHARMM
 CVFF
 Quantum mechanics is basically the molecular orbital

calculation and offers the most detailed description of a
molecule’s chemical behavior.
 HOMO – highest energy occupied molecular orbital
 LUMO – lowest energy unoccupied molecular orbital
 Quantum methods utilize the principles of particle physics to
examine structure as a function of electron distribution.
 Geometries and properties for transition state and excited
state can only be calculated with Quantum mechanics.
 Schrödinger equation: HΨ = EΨ = (U + K ) Ψ
QSAR(CO5)
Introduction
• It is said to be a mathematical relationship in the form of an

equation between the biological activity and measurable
physiochemical parameters.
• QSAR attempts to identify and quantify the

physicochemical properties of drug and to see whether any of
these property has an effect on the drugs biological
activity
QSAR(CO5)
• The parameters used in QSAR is a measure of the potential

contribution of its group to a particular property of the parent
drug.
• Activity is expressed as log(1/C).
• C is the minimum concentration required to
cause a defined biological response.
• Physicochemical property as log p.
QSAR(CO5)
Introduction
• It is said to be a mathematical relationship in the form of an

equation between the biological activity and measurable
physiochemical parameters.
• QSAR attempts to identify and quantify the

physicochemical properties of drug and to see whether any of
these property has an effect on the drugs biological
activity
QSAR(CO5)
PARAMETERS
Parameters used in QSAR studies are
1. Lipophilic parameters: partition coefficient, π-

substitution constant.(HYDROPHOBICITY)
2. Electronic parameters: Hammet constant, dipole

moment.
3. Steric parameters: Taft’s constant, molar

refractivity, Verloop steric parameter

QSAR(CO5)
A) LIPOPHILIC PARAMETERS
• Lipophilicity is partitioning of the

compound/DRUG between an aqueous and non-aqueous phase.
• Partition coefficient:
P=[drug] in octanol/[drug] in water

QSAR(CO5)

QSAR(CO5)
• Linear relationship between Log p and Log 1/C

• Activity of drugs is often related to P
• e.g. binding of drugs to serum albumin (straight line -
limited range of log P)

QSAR(CO5)

QSAR(CO5)

QSAR(CO5)
• σ value depends on inductive and resonance effects
• σ value depends on whether the substituent is meta or para
ortho values are invalid due to steric factors

• Electronic Factors R & F
 R - Quantifies a substituent’s resonance effects
 F - Quantifies a substituent’s inductive effects
• The constants σ,R and F can only be used for aromatic
substituents

QSAR(CO5)
STERIC SUBSTITUTION CONSTANT

 Taft’s steric factor (Es')
• Measured by comparing the rates of hydrolysis of substituted

aliphatic esters against a standard ester under acidic conditions
Es = log kx - log ko
• kx represents the rate of hydrolysis of a substituted ester
• ko represents the rate of hydrolysis of the parent ester

QSAR(CO5)

QSAR(CO5)
HANSCH EQUATION
• A QSAR equation relating various physicochemical properties

to the biological activity of a series of compounds
• Usually includes log P, electronic and steric factors
• Start with simple equations and elaborate as more
structures are synthesised
Typical equation for a wide range of log P is parabolic

Log1/C=-k1(log P)2 + k2 log P+k3σ+k4Es+k

QSAR(CO5)
Example: Adrenergic blocking activity of -halo--

arylamines
Y X
CH CH2 NRR'
 1
Log
C  1.22  - 1.59  + 7.89


Conclusions:
•Activity increases if  is +ve (i.e. hydrophobic substituents)
•Activity increases if  is negative (i.e. e-donating substituents)
Reference:- https://www.slideshare.net/nehla313/qsar-57546822
Reference:-https://www.slides Dr. Rakhi Mishra
chandana majee
BP 601T BP 601T
UNIT V
37
hare.net/SharadPatange2/qsar UNIT V
MOLECULAR DOCKING(CO5)
 Molecular docking is the study of how two or more molecular

structures (e.g., drug and enzyme or protein) fit together [50].
In a simple definition, docking is a molecular modeling
technique that is used to predict how a protein (enzyme)
interacts with small molecules (ligands).Docking is an attempt
to find the best matching between two molecules.

 Docking is a method which predicts the preferred orientation

of one ligand when bound in an active site to form a stable
complex.
 Docking of small molecule ligand (brown) with a protein
receptor (green) to produce a complex.
fig:- shows docking of receptor with ligand

 Molecular docking is one of the most frequently used methods

in structure based drug design, due to its ability to predict the
binding-conformation of small molecule ligands to the
appropriate target binding site. Characterisation of the binding
behaviour plays an important role in rational design of
drugs as well as to elucidate fundamental biochemical
processes.

APPLICATIONS
Docking is most commonly used in the field of drug design —
most drugs are small organic molecules, and docking may be
applied to:
•hit identification – docking combined with a scoring function can
be used to quickly screen large databases of potential drugs in
silico to identify molecules
•lead optimization – docking can be used to predict in where and in
which relative orientation a ligand binds to a protein (also referred
to as the binding mode or pose).
•Bioremediation – Protein ligand docking can also be used to
predict pollutants that can be degraded by enzymes.

TYPES OF DOCKING
I.Rigid Docking(Lock and key)
If the bond angles, bond lengths and torsion angles of the
components are not modified at any stage of complex
generation, it is known as rigid body docking. A
 The internal geometry of both the receptor and ligand are
treated as rigid.
 Ligand + receptor
Fig showing lock and key model

 Flexible Docking
 In flexible docking molecules are flexible ,confirmations of
the receptor and the ligand molecules , as they appear in
complex.
 With further increases in computational power, it became
possible to model changes in internal geometry of the
interacting partners that may occur when a complex is
formed. This type of modelling is referred to as "flexible
docking".

fig: flexible docking algorithim

Rigidity vs flexibility
 This assumption is obviously problematic and was proven to

be wrong in several cases
 Other methods try to handle the flexibility problem indirectly
or at least to “minimize the damage” of not incorporating
flexibility.
 Most of the early algorithms assumed that the docked
molecules do not change conformations. This assumption
allows to treat the molecules as rigid bodies, making the
algorithm simpler and faster

Rigidity vs flexibility
 Newer algorithms try to face the flexibility problems with

variety of ways. •Docking procedures that perform rigid body
search are termed rigid docking •Docking procedures that
consider possible conformational changes are termed flexible
docking

STAGES IN DOCKING
i) Target/Receptor selection and preparation
ii.Ligand selection and preparation
ii.Docking
iii.Evaluating docking results
Examples of Docking
1.DHFR
- Folate dependent enzyme involve in one carbon metabolism.
- Important role in DNA synthesis.
- It was targeted for cancer chemotherapy.
- DHFR catalyzes the reduction of folate and 7,8-dihydrofolate to 5,6,7,8
tetrahydrofolate(THF).
 DHFR Substrates:
 Folic acid and Dihydrofolic acid.
 DHFR Inhibitors:
I.Methotrexate

Act as an inhibitor of DHFR in the conversion of 7,8-

dihydrofolate(FtH2) to 5,6,7,8-tetrahydrofolate(FH4).
FH2
FH4
• Fig. Reduction of FH2 to FH4

Fig.human dihydrofolate reductase complexed with trimethoprim .
COMBINATORIAL CHEMISTRY(CO5)
Introduction
 Combinatorial chemistry (Combichem) is a collection of
techniques which allow for the synthesis of multiple

compounds at the same time.
• This powerful new technology has begun to help

pharmaceutical companies to find new drug candidates
quickly, save significant money in preclinical development
costs and ultimately change their fundamental approach to
drug discovery.
 Combinatorial chemistry may be defined as the systematic and

repetitive, covalent connection of a set of different “building
blocks” of varying structures to each other to yield a large
array of diverse molecular entities.
 Thus the combinatorial chemistry approach has two phases:

1.Making a library.
2.Finding the active compound
Problems/ DISADVANTAGES OF Traditional/Conventional

Synthesis:
 1 chemist 1 molecule
 Can only make one molecule at a time.
 Each synthesis very time consuming.

 Multistep synthesis have loss at each step.
 Purification of products very time-consuming between
steps.
 Yields can be low and produces very few molecules at a time
for testing, Slower lead generation.

 Hundreds of molecules in a month are generated.
 High risk of failure.
Benefits/ADVANTAGES with Combinatorial Synthesis:

• Can make multiple molecules at a time.
• The time & cost associated with the generation & analysis of
each individual molecule is significantly less when compared
to the time & cost of an individual synthesis.
• Yields can be high and produces many molecules at a time for
testing.
• Faster lead generation.
• Low risk of failure.

Principle of Combichem
To prepare a large number of different compounds at the same
time Instead of synthesizing compounds in a conventional one
at a time manner and then to identify the most promising
compound for further development by high throughput
screening (HTS).
 In combinatorial synthesis different compounds are generated

simultaneously under identical reaction conditions in a
systematic manner, so that ideally the products of all
possible combinations of a given set of starting materials
(termed building blocks) will be obtained at once. The
collection of these finally synthesized compounds is referred
to as a combinatorial library. The library is then screened for
useful properties and the active compounds are identified.
A + B AB (A) Conventional approach

+ or (B)
A1 - n B1 - n A1 – n B1 – n
Combinatorial approach
A1 B1 A1B1 A1Bn
A1B1
A2 B2 A2B1 A2Bn
A2B1
An Bn AnB1 AnB2 AnBn
(A) In a conventional synthesis one starting material A reacts

with one reagent B resulting in one product AB.
A + B AB (A) Conventional approach

+ or (B)
A1 - n B1 - n A1 – n B1 – n
Combinatorial approach
A1 B1 A1B1 A1Bn
A1B1
A2 B2 A2B1 A2Bn
A2B1
An Bn AnB1 AnB2 AnBn
(B) In a combinatorial synthesis different building blocks of type

A (A1-An) are treated simultaneously with different building
blocks of type B (B1-Bn) according to combinatorial
principles, each starting material A reacts separately with all
reagents B resulting in a combinatorial library A1-nB1-n.
Types of Combichem
Combinatorial chemistry is of two types:
• SOLID PHASE COMBINATORIAL CHEMISTRY----
Compound library synthesized on solid phase such as resin bead
• SOLUTION PHASE COMBINATORIAL CHEMISTRY
Compound library synthesized in solvent in the reaction flask
 Combinatorial chemistry is of two types:

 SOLID PHASE COMBINATORIAL CHEMISTRY
• (Compound library synthesized on solid phase such as resin

bead)
• SOLUTION PHASE COMBINATORIAL CHEMISTRY
(Compound library synthesized in solvent in the reaction flask
COMBINATORIAL TECHNIQUES
There are mainly two combinatorial techniques:
1) SPLIT & MIX SYNTHESIS/PORTIONING-MIXING
SYNTHESIS (One bead-one compound library)- Resin beads are
split into different vessels. Then reacted, shuffled, and split again.
Fig: showing parallel synthesis
.
2)PARALLEL SYNTHESIS-Each compound is synthesized in
specific reaction vessel. Each starting material is reacted with each
building block separately. Then product is split into portions,
reacted with different buildind block separately again
Fig: showing parallel synthesis
PHARMACOPHORE MAPPING(CO5)
 First introduced in 1990 by “Paul Herilich”.
 IUPAC defines a pharmacophore to be "an ensemble of steric

and electronic features that is necessary to ensure the optimal
supramolecular interactions with a specific biological target
and to trigger (or block) its biological response"
Reference:-https://www.slideshare.net/SharadPatange2/qsar-parameter 63
 A pharmacophore is a representation of generalized molecular

features including;
• a) 3D (hydrophobic groups, charged/ionizable groups,
hydrogen bond donors/acceptors)
• b) 2D (substructures)
• c) 1D (physical or biological)
• d) properties that are considered to be responsible for a desired
biological activity.
Reference:-https://www.slideshare.net/SharadPatange2/qsar-parameter 64
Model development (PHARMACOPHORE MODELING)

The process for developing a pharmacophore model generally
involves the following steps:
• 1) Select a training set of ligands – Choose a structurally
diverse set of molecules that will be used for developing the
pharmacophore model. As a pharmacophore model should be
able to discriminate between molecules with and without
bioactivity, the set of molecules should include both active and
inactive compounds.
• 2) Conformational analysis – Generate a set of low energy
conformations that is likely to contain the bioactive
conformation for each of the selected molecules.
• 3) Molecular superimposition – Superimpose ("fit") all

combinations of the low-energy conformations of the
molecules. Similar (bioisosteric) functional groups common to
all molecules in the set might be fitted (e.g., phenyl rings or
carboxylic acid groups). The set of conformations (one
conformation from each active molecule) that results in the
best fit is presumed to be the active conformation.
CLASSIFICATION
• .
APPLICATION.
PHARMACOPHORE MAPPING SOFTWARES

 Discovery studio :
 Window ® and Linux® based protein modeling software.
 Produced by Accelrys software company.
 Easy to use interface.
 Examples of the programs that perform pharmacophore based

searches are 3D search UNITY, MACCS-3D and ROCS.
 ROCS is using as shape based super position for identifying
compound that have similar shaped.
Faculty Video Links/ Youtube & NPTEL Video Links and Online
Courses Details (if any)
• Self Made Video Link:

NIL
• Youtube/other Video Links

https://a.impartus.com/ilc/#/course/154412/742
Summary
This unit is designed to impart fundamental knowledge on

the QSAR with its different type of parameters which can
be considered for the study of drug biological action .This
also covers use of docking software in finding the degree
of interaction of ligand with receptor.
By this power point presentation all parts of this unit of
syllabus has been emphasised and discussed as per the
need of syllabus
Daily Quiz
• Give the uses of QSAR
• Give definition of QSAR
• Describe QSAR parameters with classification.
• Write the application of pharmacophore modeling
• What is pharmacophore mapping
• What is combinatorial chemistry
Weekly Assignment
• Write the principle of docking technique
• What is drug design
• What is the role of QSAR study in synthetic chemistry
• Explain the method of combinatorial chemistry
• Describe methodology of pharmacophore mapping with its
application
MCQ s
1) Physicochemical parameters used in QSAR study is / are i)
partition coefficient ii) electric charge iii) solubility iv) all of the
above
2) Ligand and receptor complex formation studies are done by

technique of i) docking ii) combinatorial chemistry iii) ligand
study iv) none of the above
3) Different type of interactions involved in ligand receptor binding

is/ are i) Electrostatic forces ii) Electrodynamics forces iii) Steric
forces iv) all of the above

MCQ s
4) Solid phase and solution phase synthesis are types of i)
docking technique ii) combinatorial chemistry iii)
pharmacophore modelling iv) QSAR
5) A pharmacophore is i) stearic features of drug ii) electronic
feature of drug iii) both of the above iv) none of the above
6) One bead-one compound library is another name of i) split and
mix synthesis ii) parallel synthesis iii) molecular modelling
iv) molecular docking
7) Anchor or linker is attached to solid support by i) ionic bond
ii) covalent bond iii) hydrogen bond iv) none of the above

MCQ s
8) Strategies of molecular modeling are i) direct drug designing
ii) indirect drug designing iii) both of the above iv) none of
the above
9) Technique used to identify the most promising compound
from many compounds for further development is i) Docking
ii) HTS iii) both of the above iv) none of the above
10) Molecular modeling technique allows to study the i) 3
dimensional structure ii) 2 dimensional structure iii) planar
structure iv) crystal structure

Old Question Papers of AKTU
• Syllabus is new from this year and is according to PCI so no

old aktu paper is according to current followed syllabus
• .

Expected Questions for University Exam
• Give examples of physicochemical parameters which can be

of use for drug design approach
• Write the theory and applications of docking technique
• Define the concept of combinatorial chemistry with its
applications
• Discuss the types of combinatorial chemistry
• Define pharmacophore modeling technique used in drug
design
References and Books to be followed
Noida Institute of Engineering and Technology
(Pharmacy Institute) Greater Noida

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Noida Institute of Engineering and Technology

(Pharmacy Institute) Greater Noida

Medicinal Chemistry III

chandana majee BP 601T UNIT V

Upon completion of the course student shall be able to

Reference:-https://www.slides chandana majee BP 601T UNIT V

CO No. CO STATEMENT LEVEL OF

PO2 Planning Abilities: Demonstrate effective planning abilities

PO6 Professional Identity: Understand, analyze and

PO Environment and sustainability: Understand the impact of

Reference:-https://www.slides chandana majee BP 601T UNIT V 12

Mapping of Course Outcomes with POs

Subject covers description of various new techniques used

 Molecular modeling is define as Theoretical methods and

• Direct Drug Designing

• Indirect Drug designing

a.Molecular Mechanics (MM).

 Molecular mechanics breaks down pair wise interaction

 The molecular mechanics energy expression consists of a

 Quantum mechanics is basically the molecular orbital

• It is said to be a mathematical relationship in the form of an

• QSAR attempts to identify and quantify the

• The parameters used in QSAR is a measure of the potential

• Physicochemical property as log p.

• It is said to be a mathematical relationship in the form of an

• QSAR attempts to identify and quantify the

1. Lipophilic parameters: partition coefficient, π-

2. Electronic parameters: Hammet constant, dipole

3. Steric parameters: Taft’s constant, molar

chandana majee BP 601T UNIT V 27

• Lipophilicity is partitioning of the

chandana majee BP 601T UNIT V 28

chandana majee BP 601T UNIT V 29

• Linear relationship between Log p and Log 1/C

chandana majee BP 601T UNIT V 30

chandana majee BP 601T UNIT V 31

chandana majee BP 601T UNIT V 32

• σ value depends on whether the substituent is meta or para

ortho values are invalid due to steric factors

chandana majee BP 601T UNIT V 33

STERIC SUBSTITUTION CONSTANT

• Measured by comparing the rates of hydrolysis of substituted

chandana majee BP 601T UNIT V 34

chandana majee BP 601T UNIT V 35

• A QSAR equation relating various physicochemical properties

Typical equation for a wide range of log P is parabolic

chandana majee BP 601T UNIT V 36

Example: Adrenergic blocking activity of -halo--

 Molecular docking is the study of how two or more molecular

chandana majee BP 601T UNIT V 38

 Docking is a method which predicts the preferred orientation

fig:- shows docking of receptor with ligand

chandana majee BP 601T UNIT V 39

 Molecular docking is one of the most frequently used methods

chandana majee BP 601T UNIT V 40

chandana majee BP 601T UNIT V 41

Fig showing lock and key model

chandana majee BP 601T UNIT V 42

chandana majee BP 601T UNIT V 43

fig: flexible docking algorithim

chandana majee BP 601T UNIT V 44

 This assumption is obviously problematic and was proven to