molecular docking

to identify the interaction between receptor and ligand by use of autodock vina

1. Molecular Docking PRESENTED BY KOUSHIK DEB ID NO-48101

2. What is Docking? ultantructuralchangeught about by the interaction Prediction of the optimal physical configuration and energy between two molecules The docking problem optimizes: Binding between two molecules such that their orientation maximizes the interaction Evaluates the total energy of interaction such that for the best binding configuration the binding energy is the minimum The resultant structural changes brought about by the interaction

3. Protein-Protein Docking: Both molecules are rigid Interaction produces no change in conformation Similar to lock-and key model Protein- Ligand Docking: Ligand is flexible but the receptor protein is rigid Interaction produces conformational changes in ligand Categories of docking

4. The AutoDock Software Developed by AJ Olson’s group in 1990. AutoDock uses free energy of the docking molecules using 3D potential-grids Uses heuristic search to minimize the energy. Search Algorithms used: Simulated Annealing Genetic Algorithm Lamarckian GA (GA+LS hybrid)

5. Docking Preparation – Protein Add essential hydrogens Load charges Merge lone-pairs Add solvation parameters Write . pdbqs protein file

6. Docking Preparation – Ligand Assign charges Define rotatable bonds Rename aromatic carbons Merge non-polar hydrogens Write . pdbq ligand file

7. Docking Preparation – Grid AutoDock uses grid-based docking Ligand -protein interaction energies are pre-calculated and then used as a look-up table during simulation

8. Other Docking programs GOLD Hammerhead FLOG FlexX

9. PROTIEN MOLECULE 1 Interleukin 10:- Interleukin-10  ( IL-10 ), also known as  human cytokine synthesis inhibitory factor  ( CSIF ), is an anti- inflammatory cytokine . In humans, IL-10 is encoded by the  IL10  gene. IL-10 is a cytokine with multiple,  pleiotropic , effects in immunoregulation and inflammation. It downregulates the expression of  Th1  cytokines, MHC class II antigens, and co-stimulatory molecules on  macrophages . It also enhances B cell survival, proliferation, and antibody production.

10. LIGAND MOLECULE Alkaloids derived from tyrosine  Isoquinoline . FormulaC20H24NO4 Mol weight342.4089

11. ligand_out.pdbqt Mode | affinity | dist from best mode | (kcal/mol) | rmsd l.b .| rmsd u.b . -----+------------+----------+---------- 1 -7.0 0.000 0.000 2 -6.3 1.314 4.880 3 -6.2 31.170 33.266 4 -5.8 30.753 33.034 5 -5.7 45.037 47.694 6 -5.7 32.338 34.496 7 -5.6 39.335 42.475 8 -5.6 32.123 34.415 9 -5.5 38.760 41.802 Writing output ... done.

12. Protein molecule 2 Nuclear factor NF kappa bita is a protein that control transcription of DNA

13. mode| affinity | dist from best mode |(kcal/mol)| rmsd l.b .| rmsd u.b . -----+------------+----------+---------- 1 -5.7 0.000 0.000 2 -5.4 7.456 10.004 3 -5.3 19.915 20.850 4 -5.1 6.875 9.619 5 -4.8 8.921 12.263 6 -4.8 7.974 10.961 7 -4.7 21.984 23.127 8 -4.7 9.137 12.067 9 -4.6 20.064 21.222

14. Which docking results should I consider as likely to bind well to my target? When the results are sorted by lowest energy found for each compound, the compounds that bind as well as your positive control or better can be considered as potential hits. Remember to allow for the roughly 2.5 Kcal/mol standard error in the AutoDock scoring function. If you do not have a positive control, consider the compounds with the lowest energies as potential hits.