[ Tether | Distance Restraint | Docking Templates ]

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

16.12.1 Impose Ligand Atom Tether

To impose tethers to selected atoms of the ligand before redocking.

• Setup the ligand and receptor.
• Click on the edit tools panel button.
• Click on the impose positional restraints button.
• Select the atoms you wish to tether in the ligand.
• A table listing the tethers will be displayed and red crosses through the atom indicates a tether.
• Click on the re-dock button and the atoms selected will remain tethered in place.

About the table: The tethers can be edited and deleted using the table. Double click on a value in the table to edit it.

• Use Check "use" to use the tether in docking.
• L Toggle the tether display on or off.
• Type Type of tether "position" indicates a positional restraint (tether).
• Atom1 ICM selection language for the tethered atom. Atom 1 can also be SMARTS expression which define the atom (for both distance and position) The matched atom should be marked with '*'. For example oxygen in the double bonded to the 5-member ring in biotin can be defined as: NC(=[O*])N
• Atom2 xyz position (3 comma separated numbers)
• max dist Sets the maximum distance for the tether.
• min dist Sets the minimum distance for the tether.
• weight the overall weighting factor for the tether penalty term.
• rm Delete the tether.
• err Deviation from the position after docking.

16.12.2 Impose Distance Restraint

There are three types of distance restraint you can make:

1. lig - static rec : fixed side-chain (weighted tether)
2. lig - flex rec : flexible side-chain (drestraint)
3. lig - lig : drestrains

To impose distance restraints before redocking.

• Setup the ligand and receptor.
• Click on the edit tools panel button.
• Click on the distance restraint button.
• Select two atoms to form the distance restraint. The distance restraint can be between two atoms in a ligand or between the ligand and receptor
• A table detailing the distance restrints will be displayed and red crosses through the atom indicates a tether.
• Click on the re-dock button and the atoms selected will remain tethered in place.

About the table: The distance restraints can be edited and deleted using the table. Double click on a value in the table to edit it.

• Use Check "use" to use the distance restraint in docking.
• L Toggle the distance restraint display on or off.
• Type Type of restraint. There are three types of distance restraint
  1. lig - static rec : fixed side-chain (weighted tether)
  2. lig - flex rec : flexible side-chain (drestraint)
  3. lig - lig : (drestraint)
• Atom1 ICM selection language for the first atom in the distance restraint.
• Atom2 ICM selection language for the second atom in the distance restraint.
• max dist Sets the maximum distance for the restraint.
• min dist Sets the minimum distance for the restraint.
• weight the overall weighting factor for the distance restraint penalty term.
• rm Delete the distance restraint.
• err Deviation from the position after docking.

Note: The area within min-max distance is zero (flat-bottomed). With a weight of 1. you will have fair coverage of conformations with minor violations, going up to 5 or 10 will pretty much force the system to always stay there, below 1. you will only have a sort of weak steering force.

16.12.3 Docking Templates

You can use either substructure or Atomic Property Field Templates for docking.

First prepare the template:

• The template needs to be in the same coordinate frame as the region you are docking to. The easiest way to prepare the template is to right click on a ligand in the pocket in the ICM workspace and choose "copy to another object". Rename as template and then right click on it and choose Edit/Edit compound and delete the atoms you do not want in the template.

• Setup the ligand and receptor.
• File/Open a 3D template structure and place in the pocket.
• Click on the Edit Tools panel button.
• Click on the Impose Template Restraint button.
• Select the template object from the drop down menu and choose whether you wish to impose substructure or 3D pharmacophore APF template.
• A table will be displayed called DOCK_RESTRAINTS where you can turn the template on or off.