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
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
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.
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.