Molecular Docking
PRESENTED BYKOUSHIK DEBID NO-48101
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
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
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)
Docking Preparation – ProteinAdd essential hydrogensLoad chargesMerge lone-pairsAdd solvation parametersWrite .pdbqs protein file
Docking Preparation – LigandAssign chargesDefine rotatable bondsRename aromatic carbonsMerge non-polar hydrogensWrite .pdbq ligand file
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
Other Docking programsGOLDHammerhead FLOGFlexX
PROTIEN MOLECULE 1Interleukin 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.
LIGAND MOLECULE
Alkaloids derived from tyrosine Isoquinoline .
FormulaC20H24NO4
Mol weight342.4089
ligand_out.pdbqtMode | 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 41.802Writing output ... done.
Protein molecule 2Nuclear factor NF kappa bita
is a protein that control transcription of DNA
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
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.
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