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Contents
 
Introduction
Help Videos
Reference Guide
Getting Started
Protein Structure
Molecular Graphics
Slides & ActiveICM
Sequences & Alignments
Protein Modeling
Cheminformatics
Learn and Predict
Docking
 Small Molecule Docking
 Flexible Docking
 Template Docking
 Covalent Docking
  Sketch Reaction
 De Novo Tools
 Autofit
 Protein-Protein Docking
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12.4 Covalent Docking
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[ Sketch Reaction ]

Tutorial | Video Tutorial | Covalent Docking Webinar

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

To undertake covalent docking you should:

  • Setup the docking project (Docking/SetProject).
  • Sketch the reaction you wish to use for covalent docking. ICM has many common covalent reactions already drawn available inside ICM. If the one you need is available you can select it in the Docking/Covalent step below. You can see the reactions in ICM by opening the file Covalent_Mechanisms.icb in the ICM distribution directory on your computer.
  • 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 the button "Load Preset Reactions" or use the drop down menu called "Source Reaction Library" to select the table containing the reaction(s) you sketched.
  • Select the reactions you need by clicking on them - thry should be shaded grey if selected.
  • Click on the Add to List and this will move them to the left hand panel. You can remove reactions by right clicking on the row number and choosing delete.
  • Make sure the "Remake Maps Immediately" button is checked.
  • Click OK.

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.


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