Quantitative StructureActivity Relationship (QSAR)

Quantitative StructureActivity Relationship (QSAR)

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 Presentation out line

Introduction
History of QSAR
requirement for good QSAR model
Common QSAR Modeling Errors
Procedure of QSAR
QSAR methods
Applications QSAR
Disadvantage QSAR

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 Introduction

A QSAR is a mathematical relationship between

a biological activity of a molecular system and
its geometric and chemical characteristics.
A QSAR is a statistical model that relates a set of
structural descriptors of a chemical compound to
its biological activity.
QSAR attempts to find consistent relationship
between biological activity and molecular
properties, so that these rules can be used to
evaluate the activity of new compounds.

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 Introduction

QSAR relate structure to any physical-

chemical property of molecule
Specific to some biological/pharmaceutical
function of molecule (Absorption,
Distribution/Digestion, Metabolism,
Excretion).

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 Introduction

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 History of QSAR

Russian chemist who arranged the 63 known

elements into a periodic table based on atomic
mass, which he published in Principles of
Chemistry in 1869. Mendeleev left space for new
elements, and predicted three yet-to-be-
discovered elements: Ga (1875), Sc (1879) and
Ge (1886).

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 History of QSAR

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 History of QSAR

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 History of QSAR

Corwin Herman Hansch (1918 2011) is The

father of the concept of quantitative
structureactivity relationship (QSAR), the
quantitative correlation of the physicochemical
properties of molecules with their biological
activities.

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 History of QSAR

The first application

Generation of an equation
A.Biological activity: minimum effective dose
B.Descriptors
- Electronic characteristics
- hydrophobicity
Eg. Log1/c k1logP K2 (logP)2 +k3 +k4
Where, C = minimum effective dose
P = Octanol-water partition coefficient
= Hammett substituent constant
Kx = constants derived from regression analysis

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 History of QSAR

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 Why do we need QSAR models?

All chemical substances need to be tested in terms of their

toxicological and environmental properties before their use
There are several reasons to use QSAR Models : very fast,
often free, reduce the number of animals used in
experiments
Chemical science and industry are moving rapidly from
making relatively simple molecules, one at a time, to
generating large libraries of molecules, that may be large,
complex, and hybrid materials with exotic properties.
(e.g. nano particles).

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 Why do we need QSAR models?

High throughput measurement of the physical, chemical,

biological and environmental properties of nanoparticles
will allow hazard estimation of in the medium term.

We are moving rapidly from a data poor to data rich

environment new methods required to extract information
and knowledge from large data sets and predict properties
of new (nano)materials.

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 Why do we need QSAR models?

Quantitative structure-property relationship (QSPR)

modelling is asuite of techniques for performing this type
of modeling.
QSAR has been widely used to predict the toxicity of
substances in bulk form (especially druglike compounds)
but, up to date, QSAR studies for the prediction of
nanoparticle toxicity have been rarely reported.
QSAR models are very useful in case of the classic
chemicals but the concept of nanoQSAR is still under
development.

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 Why do we need QSAR models?

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 purpose of QSAR
To predict biological activity and physicochemical
properties by rational means
To comprehend and rationalize the mechanisms of action
within a series of chemicals
Savings in the cost of product development
Predictions could reduce the requirement for lengthy and
expensive animal tests.
Reduction of animal tests, thus reducing animal use and
obviously pain and discomfort to animals
Other areas of promoting green and greener chemistry to
increase efficiency and eliminate waste.

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 problem we face

The reliable QSAR predictions are

limited generally to the chemicals that
are structurally similar to ones used to
build that model.

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 problem we face

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 What is required for good QSAR model?

The QSAR model should meet the requirements of the OECD

principles .
a defined endpoint
an unambiguous algorithm
a defined domain of applicability
appropriate measures of goodness of fit, robustness and
predictivity
a mechanistic interpretation if possible.

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 Common QSAR Modeling Errors

Uninformative descriptors
Poor descriptor selection and chance correlations
Modeling complex, nonlinear structure property
relationships with linear models
Incorrectly validating QSPR models
Not understanding the domain of applicability of models

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 Methods

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 Molecular Descriptors

Molecular descriptors can be defined as a numerical

representation of chemical information encoded within a
molecular structure via mathematical procedure. Type of QSAR
is based on the dimensionality of molecular descriptors used :

0D These are descriptors derived from molecular formula e.g.

molecular weight, number and type of atoms etc.

1D A substructure list representation of a molecule can be

considered as a one-dimensional (1D) molecular representation
and consists of a list of molecular fragments (e.g. functional
groups, rings, bonds, substituents etc.).

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 Molecular Descriptors

2D A molecular graph contains topological or two dimensional

(2D) information. It describes how the atoms are bonded in a
molecule, both the type of bonding and the interaction of
particular atoms (e.g. total path count, molecular connectivity
indices etc.).
3D These are calculated starting from a geometrical or 3D
representation of a molecule. These descriptors include
molecular surface, molecular volume and other geometrical
properties. There are different types of 3D descriptors e.g.
electronic, steric, shape etc.
4D In addition to the 3D descriptors the 4th dimension is
generally in terms of different conformations or any other
experimental condition.

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 Molecular Descriptors

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 Data Mining Methods
A relatively new field which share some techniques with
traditional data analysis but also brings a lot of new
visions and techniques

DM is the discovery of useful Information and Knowledge

from a large collection of Data, in order to help the
Decision

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 Data Mining Methods

Data: records of numerical data, symbols,

images, documents
Knowledge: Rules: IF .. THEN ..
- Causeeffect relationships
- Decision trees Patterns:
- abnormal, normal operation
- Predictive equation making

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 Data analysis Methods

Different Statistical Methods have been used in QSAR for the

extraction of useful information from the data.

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 Data analysis Methods

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 Application of QSAR

QSAR is important in drug development as

it provide quantitative information relating
properties of a compound to its activity.
QSAR provides a cost effective means of
modifying drug molecules by in silico
design and enhancement.
It quantifies the relationship between
structure and activity which provides an
understanding of the effect of structure on
activity.

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 Application of QSAR

There is also the potential of make

predictions leading to the synthesis of novel
analogous.
Care must be taken not to use extrapolation
outside the range of the data set.
The result of QSAR can be used to help
understanding interactions between
functional groups in the molecules of
greatest activity with those of their target.

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 Application of QSAR

There are a large number of applications of these

models within industry, academiac and
governmental (regulatory) agencies.
The estimation of physicochemical properties,
biological activities and understanding the
physicochemical features behind a biological
response in drug design.
The rational design of numerous other products
such as surfaceactive agents, perfumes, dyes, and
fine chemicals.

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 Application of QSAR

The prediction of a variety of

physicochemical properties of molecules.
The prediction of fate of molecules which
are released into the environment.
The identification of hazardous compounds
at early stages of product development, the
prediction of toxicity to humans and
environment.

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 Application of QSAR

Equations are produced to predict relationship

that properties may have on the
mechanism/distribution of drug.
It is used for the prediction of biological activity.
QSAR include regression, pattern recognition
techniques.
QSAR is an equivalent to chemometrics or
multivariate statistical data analysis.

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 QSAR disadvantages

False correlation may arise through too heavy reliance

being placed on biological data.
Experiments upon which QSAR analysis depends lack
design in the strict sense of experimental design.
Many QSAR results cannot be used to confidently predict
the most likely compounds of best activity.
Various physiochemical parameters are known to be cross
correlated. Therefore, only variables or their combinations
that have little covariance should be used in a QSAR
analysis.

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THANK YOU!!

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