Quantitative structure -QSAR modeling on a set of structurally related chemicals refers to the development of a mathematical correlation between a chemical response and quantitative chemical attributes defining the features of the analyzed molecules. Descriptors (parameters) in QSAR are “the ‘numerical values associated with the chemical constitution for correlation of chemical structure with various physical properties, chemical reactivity or biological activity.” Properties of ideal descriptor: 1. A descriptor should be relevant to a broad class of compounds. 2. A descriptor must be correlated with the studied biological responses while illustrating insignificant correlation with other descriptors. 3. Calculation of the descriptor should be fast and independent of experimental properties. 4. A descriptor should produce different values for structurally dissimilar molecules even if the structural differences are little. 5. A descriptor should possess physical interpretability to determine the query features for the studied compounds.

1. QSAR
1

2. Quantitative SAR
Means which can be quantified
or given a value.
Relationship between the
structure of the chemical and
the biological activity.
Quantitative structure -QSAR modeling on a set of structurally related chemicals refers to the
development of a mathematical correlation between a chemical response and quantitative
chemical attributes defining the features of the analyzed molecules.
2

6. Free Wilson Model
( de novo model )

7. 1. In any chemical skeleton of drug, if
same substitution at same position ,
then biological activity will be constant.
N
R1
CO
N
R2 R3

8. 2. A particular substituent in a specific
position is assumed to make an additive
and constant contribution to the biological
activity of a molecule.
𝐵. 𝐴. = 𝜇 + 𝑎𝑖𝑗
Where,
B.A. = biological activity of the molecule
𝜇 = biological activity of the unsubstituted compound ( skeleton )
a = constant
i = no. of position at which substitution occurs
j = no. of substituent at that position

9. Hammett approach

10. Depends upon ; Electronic effect of molecule
- Similar compounds react similarly
- Similar changes in structure causes similar changes in reactivity
log 𝐾𝑥
𝐾𝐻 = ρσ
Where,
Kx = ionisation constant
KH = hydration constant
ρ = reaction constant
σ = electronic constant / hammett constant

12. Taft approach

13. Acidic hydrolysis = steric effect
Basic hydrolysis = steric + electronic parameter
σ* = 1
2.48 [ log( 𝐾𝑥
𝐾𝐻 ) b – log( 𝐾𝑥
𝐾𝐻 ) a ]
Where,
a = acid
b = base

14. Hansh analysis

15. Concept 1 : Random walk
From the point of administration to site of action the drug has
to cross several lipid aqueous barriers to reach critical reaction
site

16. Concept 2 : the concentration of drug reaching to
the site of action is directly proportional to it’s
activity
Concept 3 : the attachment of drug to its target
protein
log
1
𝑐
= 𝐾1𝜋 + 𝐾3𝜎 + 𝐾4𝐸𝑆 + 𝐾5

17. Biological
activity
Log P

18. Craig plot

20. Topliss scheme

22. FORMALISM(the mathematical logic)
Biological Activity= f(Chemical Attributes)
Response= f (chemical structure, physicochemical
property)
Y = a0 + A1x1 + a2X2 + a3X3 + ……… +
anXn
= f
(descriptors)
22

23. DESCRIPTORS(PARAMETERS)
“They are the ‘numerical values associated
with the chemical constitution for correlation
of chemical structure with various physical
properties, chemical reactivity or biological
activity.”
23

24. Common parameters
PARAMETERS
Electronic
Hammett
Constant
Taft’s Substituent
Constant
Inductive
substituent
constant
Steric
Molecular
connectivity
Van der Waals
dimension
Minimal steric
difference
Partition
Coefficient
Hansch
substituent
constant
Fragmentation
Constant
Chromatographic
Rm Value
Biological
Relationship
Hansch Analysis
Fergusion effect
Free Wilson
Analysis
24

25. 25
Dimensional Classification of descriptors

26. Properties of ideal descriptors
1. A descriptor should be relevant to a broad class of compounds.
2. A descriptor must be correlated with the studied biological responses while
illustrating insignificant correlation with other descriptors.
3. Calculation of the descriptor should be fast and independent of experimental
properties.
4. A descriptor should produce different values for structurally dissimilar molecules
even if the structural differences are little.
5. A descriptor should possess physical interpretability to determine the query
features for the studied compounds.
26

27. How The Descriptor Are Quantified or
Calculated?
Theoretical Method Experimental method
27

28. How we can find the descriptors for the
structures we already know?
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By Using Software
SOFTWARE Links
Cerius2 http://accelrys.com/
PaDEL-Descriptor http://padel.nus.edu.sg/software/padeldescriptor/
E-Dragon at VCCLAB http://www.vcclab.org/lab/edragon/
MOLE db http://michem.disat.unimib.it/mole_db/
ChemDes http://www.scbdd.com/chemdes/

29. Mathematical tools used for QSAR:-
1. Simple Linear Regression Analysis
2. Multiple Linear Regression Analysis
3. Stepwise Linear Regression Analysis
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30. 30
Demo of Simple linear regression.

31. 31

32. 32

33. 33

34. 34

35. 35
Thankyou