online documentation

Molecular docking is a method that attempts to assess the binding affinity of a ligand to a particular target (protein, DNA, carbohydrates, lipids, etc.). Typical high-throughput docking tools handle the ligand flexible while the protein remains rigid.

Docking mainly consists of the following two steps: (i) pose generation, (ii) affinity prediction (scoring). During pose generation, the ligand is placed into the binding site by sampling its rotational and translational degrees of freedom of the ligand. Subsequently, the affinity is estimated based on the generated pose.

Docking tool: AutoDock Vina (1.1.2).

In the mcule Docking (Vina) filter you can:

1. select target structure from sc-PDB
   • select from among ~10,000 PDB structures automatically prepared for docking
   • search for PDB ID, Protein name, Organism name, UniProt Name/Accession ID/Taxonomic ID
   • automatic preparation involves: adding hydrogens if none exists in input file; adding Gasteiger charges; merging charges and removing non-polar hydrogens, lone-pairs, water molecules and non-standard residues
   • automatic preparation is done by AutoDockTools
   • centre of the binding site is automatically determined based on the position of the co-crystallized ligand
2. upload target structure (will be available soon)
   • target structures can be uploaded in pdb, pdbqt or mol2 files by clicking on “Manage files”
   • uploaded files can be selected for docking
   • automatically prepare your target
3. select the X, Y, Z binding site coordinates (AutoDockTools can help to identify the centre of the binding site of your target)
4. select the binding site area (default is 22 Angstroms)
5. select the exhaustiveness parameter of conformational sampling (range: 1-8; default: 2)
6. select the maximum number of conformers to be generated (range: 1-9; default: 1)

Target structures selected from sc-PDB or uploaded are prepared for docking by AutoDockTools. For uploaded structures the user can choose to opt out the automatic preparation. In this case we still check the validity of the input. After the target has been prepared for docking, input ligands are prepared. Docking requires input ligands with a valid 3D structure. Unknown or undefined tetrahedral stereo centres are converted into well-defined ones by the stereoisomer generator of mcule. The input ligand collection is prepared for docking. Molecules failed to dock are skipped. To ensure that molecule conversions didn't affect the identity of the molecule, InChI strings of the docking input and output are compared and results are discarded in case of InChI mismatch.

The output of the Docking (Vina) filter is a collection of conformers. It includes the generated binding poses of the successfully docked molecules. Docking score is displayed in both list and table views by default. The docking score of AutoDock Vina is a (very rough) estimation of the binding affinity. More negative docking scores suggesting higher affinity.

For testing the Docking (Vina) functionality you can either select a target structure from the filter itself, or use the following prepared pdbqt file:

Human dopamine D3 receptor

Binding center:
X: 0.09
Y: -14.83
Z: 10.43

Binding site (Angstrom):
X: 22
Y: 22
Z: 22