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12.4 Covalent Docking

[ Sketch Reaction ]

Tutorial | Video Tutorial

Available in the following product(s): ICM-Pro | ICM-VLS |

To undertake covalent docking you should:

  • Setup the docking project (Docking/SetProject).
  • Setup the receptor (Docking/Setup Receptor) - you can remove the check mark in the "Make Receptor Maps Immediately" option because for covalent docking the maps are made at a later stage.
  • Select the residue that will be modified (makes covalent bond) in the docking project receptor (e.g. mydock_rec).
  • Choose the menu option Docking/Covalent and a dialog window as shown below will be displayed.

  • Make sure you have selected the modification residue in the docking project receptor (e.g. mydock_rec).
  • You can use the in built reactions by clicking on "Load Default Reactions" button.
  • Select the reactions you need by clicking on them or choose "Use All Reactions". You will notice a new chemical table will be displayed called "Covalent Mechanisms".

NOTE: If the reaction you need is not included in our default selection you will need to sketch the reaction as described here. The docked ligands need to match the reactants (e.g. lactam ring).

  • Next read in an SDF file containing the chemicals you wish to dock that match the reactant of the reaction.
  • To dock the ligands choose Docking/Dock from Table.

To turn off covalent docking:

  • Docking/Covalent docking and check the option "Turn off Covalent Docking".

12.4.1 Sketch a Reaction

NOTE: Save time! Please check the in-built reactions in ICM to check if your reaction has already been drawn.

In this example we are sketching the general reaction equation for acylation of a serine side-chain by beta-lactam:

Open the ICM Molecular Editor.

Sketch the reactant and product.

Note: The reaction table may contain multiple reaction mechanisms, in which case the system will try to apply them sequentially to the ligand, until first matching reaction is found. This is useful if ligands with different types of 'warheads' (reactive groups) will be considered.

Important! The top two atoms in the product which correspond to the modified serine residue need to be labeled to match the residue. In this example the atoms are labeled ca and cb.

Append the reaction to a chemical spreadsheet (table). If you want to view the atom labels (ca, cb) please select the mol column and choose "Chemical View Options" > "Show Full Atom Names".

You can check if your reaction matches the chemical(s) you are going to dock by:

  • File/Open and read in the chemical sdf file you are going to dock.
  • Right click on the reaction you sketched and choose "Apply Reaction".
  • Select the chemical table of the chemicals you are going to dock.
  • Click on enumerate.
  • If the reaction matches the chemicals you are going to dock then you should see a new table called T_react.

Once the reaction has been sketched you can start the covalent docking procedure.

Template Docking

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