“Molecular docking has never been easier!”
Docking predicts the binding orientation and affinity of a ligand to a target. 1-Click Docking is the easiest molecular docking solution online.
When you are looking for the binding mode or docking score of a particular ligand, 1-Click Docking is an ideal solution to start with. It typically gives you good insights about how your ligand can bind to the target: what critical interactions it forms at the binding site. One step forward is to use the Docking (Vina) filter and dock multiple ligands into a single target.
1-Click Docking is extremely easy to use: draw your input ligand, select your docking target and click on Dock!
The best binding poses are listed together with their docking scores. More negative values indicate higher binding affinity. Binding poses can be displayed (“Visualize pose” button) and downloaded (“Download pose” button).
1. Conversion of input ligands defined by mcule IDs, SMILES or InChI strings to 2D MOL
mcule ID input: the mcule structure registration system automatically associates 2D MOL files with mcule IDs, therefore 2D MOL files can be easily retrieved.
SMILES input: SMILES string is first converted to canonical SMILES and then to 2D MOL file by Indigo. Next we generate a canonical SMILES from the 2D MOL file and check if the two generated canonical SMILES are identical. In case of a mismatch, the ligand is skipped.
InChI input: only standard InChIs are accepted. 2D MOL files are generated with OpenBabel. Next we generate a new standard InChI from the 2D MOL file and check if the two generated standard InChIs are identical. In case of a mismatch, the ligand is skipped.
2. Generation of defined stereoisomers
Unknown or undefined tetrahedral stereocenters and cis-trans double bonds are converted into well-defined centers and double bonds by the stereoisomer generator of mcule.
3. Conversion of ligand 2D MOL to 3D MOL
Conversion is carried out by OpenBabel (free and basic plan) or with ChemAxon's Conformers plugin (advanced and ultimate plan). To ensure that molecule conversions did not affect the identity of the molecule, InChI strings of the input ligand and output conformer are compared and in case of InChI mismatch, the ligand is skipped. If the conformer generation fails due to InChI mismatch, another defined stereoisomer is generated in step 2 (if possible).
4. Conversion of ligand 3D MOL to PDBQT
Input ligands are converted to pdbqt format by using AutoDockTools (prepare_ligand4.py) with default parameters.
5. Preparation of docking targets
Nearly 10,000 target structures integrated from the sc-PDB database (Meslamani J, Rognan D, Kellenberger E. Bioinformatics. 2011, 27, 1324-6) have been automatically prepared by AutoDockTools (prepare_receptor4.py) using default options, except:
[-e]: delete every nonstd residue from any chain
Uploaded targets can be subjected to automatic preparation (as described above).
Otherwise, PDBQT files are generated by the following options:
-A “None” (do not make any repairs)
-C (preserve input charges ie do not add new charges)
-U “None” (no clean-up)
Docking calculations are carried out by AutoDock Vina with default parameters. The best four docking poses are stored. To ensure that the identity of the molecule is not modified during docking InChI strings of the input ligand and output conformer are compared and in case of InChI mismatch, the results are discarded.