3D molecular descriptors for 3D QSAR. Physical significance and meaning of descriptors are important. QSAR should be reliable and reproducible Drug Discovery

1. How 3D structures to
be considered for
3D QSAR?
Girinath G Pillai, PhD
@giribio

2. ● Slides contains contents/pictures/videos taken from web, articles,
lectures, tutorials and its respective authors own their copyrights.
Technical Slides : slideshare.net/giribio
Case Studies : youtube.com/giribio
Workflows & Notebooks : github.com/giribio

3. - 2D to 3D using tools -
* 3D X-Ray Structures from CSD *
< 3D from Conformational Analysis >
:: 3D poses from Docking Results ::

4. The Concerns!
3D Structures
● MM or MD or DFT or
SemiEmp
● Conformational
Sampling
● Pharmacophore Maps
● Binding Affinity - 3D
poses from docking
● X-Ray 3D from CSD
● TS
3D Descriptors
● Quantum Chemical
● Electronic
● Hydrophobic
● Pharmacophore
● Steric, vdW, Electrostatic
● Polarizability
● Molecular Field
● Molecular Similarity Indices
● Topological Distance
● PPSA/PNSA
● Moment of Inertia
● WHIM, RoG
● Ionization Potential
Other Descriptors
● Derived 3D
descriptors from
other calculations
● Experimental
● Others

5. Factors to consider
Property/Activity
Biological Activity
Physical Property
Chemical Property
Pharmacokinetic
Materials Property
Toxicity
others….
Source of 3D data
2D & 3D databases
Binding DB
CSD
Best poses from docking
Best conformer
Best Pharmacophore
Converged & Fully optimized
DFTs / Semi Emp.
Check all structures
Descriptor Calculation
Retain 3D geometry or not?
Generate 3D and calculate
Generate relevant descriptors
Rather calculating 1000s
Direct and Derived descriptors
Reliability
Why not 1D, 2D and others?

6. Views & Opinions
Understand the existing knowledge
Tutorials are just ‘How to do’ but not about
‘What to take care?’ - We should take care!
Good relationship between property/activity &
descriptors
Physical Significance/Meaning
Relevant descriptors NOT 1000s of descriptors
Avoid duplicates & intercorrelated descriptors
Check reliability of data used
GIGO - Beware!

7. Thanks!
@giribio
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