How 3D structures to be considered for 3D QSAR?
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3D molecular descriptors for 3D QSAR. Physical significance and meaning of descriptors are important. QSAR should be reliable and reproducible Drug Discovery
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How 3D structures to be considered for 3D QSAR?
- 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 Forum Discussion & Contributors Mentors, Students and Feedbacks Next topic: How to choose PDB for Docking? Role of Mol. Descriptors? Couldn’t get into an academic institution (of ur choice) to teach? Try teaching everyone online!