The document discusses docking, which predicts the optimal binding configuration between two molecules by optimizing their orientation and interaction energy. It describes protein-protein docking where both molecules are rigid, and protein-ligand docking where the ligand is flexible but the protein is rigid. It also discusses the AutoDock software, which uses grids and heuristic search algorithms like genetic algorithms to model docking. It provides examples of docking interleukin-10 to an alkaloid ligand, and nuclear factor kappa-B to a ligand. The document advises considering compounds with binding energies close to or better than a positive control as potential hits.

1. 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. 1. Protein-Protein Docking:
 Both molecules are rigid
 Interaction produces no change in conformation
 Similar to lock-and key model
2. 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

9. Other Docking programs
GOLD
Hammerhead
FLOG
FlexX

10. PROTIEN MOLECULE 1
Interleukin 10:-
Interleukin-10 (IL-10), also known as human cytokine
synthesis inhibitory factor (CSIF), is an anti-
inflammatorycytokine. 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.

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

12. 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.

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

15. 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

17. 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.