To modify a terminal atom with a chemical group:

• Select display tab and the use the "change hydrogen display style" button to select "display all hydrogens."
• Select the ligand tab
• Click on the "modify a terminal atom with chemical group" button.
• Click on the terminal atom you wish to modify.
• Select the group from the drop-down list or sketch it using the molecular editor button.
• Select OK
• Select the "Minimize Ligand" button.
• Re-evaluate the energy using "Recalculate Energy" button.
• If you are not happy with the modification you can use the undo button.
• If you are happy with the modification you may want to save the ligand in a molecular table. Click the add current ligand to table button.

To add a heavy neighbor

• To add a heavy neighbor (carbon atom) click on the "Heavy Neighbor" button and then click on the atom you wish to add it to.
• Select the "Minimize Ligand" button.
• Re-evaluate the energy using "Recalculate Energy" button.
• If you are not happy with the modification you can use the undo button.
• If you are happy with the modification you may want to save the ligand in a molecular table. Click the add curren t ligand to table button.

To change atom properties:

• Click on the "Change Atom Properties" button
• Click ont the atom you wish to change.
• You can change the atom type and charge.
• Click OK.
• Select the "Minimize Ligand" button.
• Re-evaluate the energy using "Recalculate Energy" button.
• If you are not happy with the modification you can use the undo button.
• If you are happy with the modification you may want to save the ligand in a molecular table. Click the add curren t ligand to table button.

To change bond type

• Select two atoms in the ligand using the atom pick button.
• Click and hold the "Change Bond Type" button
• Select bond type.

To edit the ligand in 2D:

• Click on the "Edit Ligand in 2D" button.
• Make changes using the ICM Molecular Editor.
• In the molecular editor choose File/Save and Quit.

To insert a linker between two fragments

• Select two atoms in the ligand using the atom pick button.
• Click on the "Insert Linker Fragment" button.
• Select linker.

Find best replacement group for selected atom

• Select the atom you want to add a new replacement group to.
• Click on the "Find best replacement group for selected atom" button.
• A dialog box as shown below will be displayed. Select whether you want the substituent score only to be evaluated (quick) or the full binding score.
• Select whether you want to screen the modifying groups built into ICM (see sarray of smiles called LIGAND.modifiers) or a table of your own modifier groups. If you choose your own table you will need to load the table (sdf file) into ICM and enter the name of the table into this dialog box or you can add modifiers to the sarray of smiles called LIGAND.userModifiers.

• ICM will add each fragment to the target atom and sample the energy and return a table ranked by score (see below).
• Click in the box highlighted below to see the substituent bound.

To delete atoms or bonds:

• Select a single atom using the pick atom tool and press the delete atom button. To delete a bond select the two atoms making the bond and then select the delete bond button.

NOTE: You can always use undo button to remove a bond or atom that you have made.