Chemical Functional Descriptors 2

Paper No.
: 06 Computational Biology
Module : 09 Chemical Functional Descriptors - II
Principal Investigator: Dr. Vibha Dhawan, Distinguished Fellow and Sr. Director
The Energy and Resources Institute (TERI), New Delhi
Co-Principal Investigator: Prof S K Jain, Professor,

Jamia Hamdard University, New Delhi
Paper Coordinator: Dr. Indira Ghosh, Professor

Jawaharlal Nehru University, New Delhi
Content Writer: Dr. Indira Ghosh, Professor

Jawaharlal Nehru University, New Delhi
Paper Reviewer: Dr. Debasisa Mohanty

National Institute of Immunology, New Delhi
Computational Biology
Biotechnology
Chemical Functional Descriptors - II
Description of Module
Subject Name Biotechnology
Paper Name Computational Biology
Module Name/Title Chemical Functional Descriptors - II
Module Id 09
Pre-requisites
Objectives
Keywords
Biotechnology
P06-module 9 : Chemical Descriptors
The topics will discussed what are Descriptors , how to derive Descriptors from chemical
structures,2D later we shall find how to construct 3D structure
What kinds of properties are relevant to biological functions? We shall start with 2D
descriptors, like using SMILES to chemical structure and then derive the descriptors. Just by
counting atoms we can get MW which is very effective descriptors, similarly counting many
important properties like hydrogen bond donors/acceptors, aromatic rings, rotatable bonds
etc. will provide good correlation with molecule’s biological functions. From such simple
descriptors we can proceed to find more complicated like topological and electronic
descriptors, these are found to be highly correlated to the physico -chemical properties of the
chemicals. Descriptors are chemical characteristic of compounds which explain the relevant
biological properties. Many structure based descriptors available, but molecular descriptors
are also very important like cLogP , which is directly connected with the hydrophobic
property of molecule.
Topological Descriptors are derived from structural connectivity as shown in figure here for
Tyrosine. Connection table or Distance matrix are also used as topological descriptors.
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13
OH
11 9
12 8
6
CH2
5
H2N CH
4
O OH
3 1
• 1 2 3 4 5 6 7 8 9 10 11 12 13
1.O 1 2 2 3 3 4 5 6 7 6 5 8
2.1 C 1 1 2 2 3 4 5 6 5 4 7
3.2 1 O 2 3 3 4 5 6 7 6 5 8
4.2 1 2 C 1 1 2 3 4 5 4 3 6
5.3 2 3 1 N 2 3 4 5 6 5 4 7
6.3 2 3 1 2 C 1 2 3 4 3 2 5
From this connectivity matrix one can derive Weiner Index which has strong correlation with
7.4 3 4 2 3 1 C 1 2 3 2 1 4
boiling point of alkanes. It is given by ,
8.5 4 5 3 4 2 1 C 1 2 3 2 3
9.6 5 6 4 5 3 2 1 C 1 2 3 2
10. 7 . 6Similarly 7 Zagreb
5 6index4can 3also be2derived
1 from C each1 non-hydrogen
2
atom, add1up the squares of the number of connections to other non-hydrogen atoms
11. 6 5 6 4 5 3 2 3 2 1 C 1
(regardless of bond order) and given by
2
12. 5 4 5 3 4 2 1 2 3 2 1 C
3 A few examples are worked out in slides.
13. 8 7 8 6 7 5 4 3 2 1 2 3
O
Electronic descriptors depict the property related to valence of bonded atoms, like value
which is given byh where  is count of electrons in sigma orbital and h is count of
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bonded hydrogen atoms. Simple descriptors like this explains many electronic behaviour
of the molecule like The count of adjacent atoms excluding hydrogens , count of sigma
electrons on an atoms excluding H, count of bonds joining to an atoms excluding H and
immediate topological environment of the atom in the molecule, so many important
characteristics are included in one descriptor , this explains why using descriptors one can
correlate many biological property of chemicals.
There are 4 quantum numbers as defined in the slides and a very important descriptor
called Kier-Hall electronegativity value can be derived from this quantum numbers.
From molecular connectivity some more important indices can be derived which
quantifies the shape & structure of chemicals. The Kappa shape indices are the basis of a
method of molecular structure quantification in which attributes of molecular shape are
encoded into three indices (Kappa values). These Kappa values are derived from counts
of one-bond, two-bond and three-bond fragments, each count being made relative to
fragment counts in reference structures which possess a maximum and minimum value
for that number of atoms. Many such descriptors are discussed in the slides and relevant
biological relationships are shown.
Some other molecular properties are also used as descriptors like clogP, which is octanol-
water partition coefficient; this has been found very useful in predicting the
bioavailability of a drug. Because a drug needs to be soluble enough in lipid to be able to
cross cell membranes but soluble enough in water not to get stuck there, many methods
have been proposed for calculating appropriate estimation of this property from
structures. One such starting estimation was proposed by Corwin Hansch and Al Leo at
Pomona College using a good set of chemicals whose clogP experimentally known and
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using the fragment method a statistically relevant correlation was developed. Later many
such methods are developed.
Atom based descriptors are also been very effective to predict molar refractivity, charged
partial surface area and intestinal absorption of drugs.
It is noted that seminal works were done to convert from simple SMILES to a 3D
structure depictions by several SW like CONCORD (Texas, 1987), CORINA
(Munich/Erlangen, 1990) & OMEGA ( Open Eye , ~2000 ). Each of them use very
elegant methods to convert the chemical 2D structure into perfect stereochemically
distinct and flexible 3D structures, however x-ray crystallography on small molecules are
already been collected and available with Experimental data in Cambridge Structure
Database.
Milestones in molecular modeling & Chemoinformatics came due to the ligand based
superposition of active site; it is common that if the different compounds bind to the same
active site, they must have a kind of 3D superposition. It can be by the structural
superposition as shown in some cases, but more appropriately it needs to be similar by
complementary interactions (pharmacophore feature based ) occurring at the active site,
so a substructure based searching became quite relevant. More important method was
developed which takes care of the interaction energy surrounding the molecules which
bind to the same active site, it is called comparative molecular field analysis driven
superposition of ligands.
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Similar approach also has been seen using graph similarity in the structural superposition
amongst different size of proteins .An example of such case has been shown here. Similar
computational tools are used for ligand superposition and protein superposition.
One exercise has been given for students to learn and verify the SMILES depiction, this
can be used for different descriptor calculations.
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Paper No.

Module : 09 Chemical Functional Descriptors - II

Co-Principal Investigator: Prof S K Jain, Professor,

Paper Coordinator: Dr. Indira Ghosh, Professor

Content Writer: Dr. Indira Ghosh, Professor

Paper Reviewer: Dr. Debasisa Mohanty

Paper Name Computational Biology

Module Name/Title Chemical Functional Descriptors - II

structures,2D later we shall find how to construct 3D structure

electrons on an atoms excluding H, count of bonds joining to an atoms excluding H and

immediate topological environment of the atom in the molecule, so many important

correlate many biological property of chemicals.

method of molecular structure quantification in which attributes of molecular shape are

biological relationships are shown.

bioavailability of a drug. Because a drug needs to be soluble enough in lipid to be able to

such methods are developed.

partial surface area and intestinal absorption of drugs.

structure depictions by several SW like CONCORD (Texas, 1987), CORINA

elegant methods to convert the chemical 2D structure into perfect stereochemically

superposition as shown in some cases, but more appropriately it needs to be similar by

complementary interactions (pharmacophore feature based ) occurring at the active site,

can be used for different descriptor calculations.

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