The ICM Ligand Editor allows for the modification of ligands in both 2D and 3D, with real-time assessment of the impact of these modifications on the ligand’s binding energy to the receptor. For instance, a simple click on the screen can change a substituent, and the software instantly calculates the modified ligand’s binding score. These changes can be saved, and there is an undo and redo functionality. Chemists can tag and store modified ligands in a chemical spreadsheet if they find the changes favorable. The predictions rely on MolSoft’s highly accurate ICM docking software.

The software offers a comprehensive range of tools for constrained docking, including tethers, distance restraints, fragment docking, and covalent docking. It also provides options for explicit flexibility in side chains and the ability to dock multiple ligands to account for induced fit. The ligand editor is versatile and can be used for 3D pharmacophore ligand design, employing Atomic Property Fields.

Key feature of interactive 3D ligand editor

Some of the key features of the 3D ligand editor include:

1. Interactively editing a ligand bound to a receptor
2. Edit ligand in 2D or 3D and see the effect on ligand binding
3. Change atom and bond types, switch stereo, cis and trans
4. Delete atoms and bonds
5. Rotate torsion angles
6. Sample one or more substituents
7. Screen a database of substituents to a specific atom of a ligand
8. Save new ligands in a chemical spreadsheet, export to Excel, SDF, Mol or PDB format
9. Convenient undo and redo modification feature
10. Modification history table: Every ligand modification is stored and recorded in a chemical spreadsheet. Double-click on the spreadsheet to view the change.
11. Hetero atom scan around ligand: This option allows you to scan groups and hetero atoms at multiple locations on the ligand.
12. R-group scan around ligand: This option allows you to scan groups and hetero atoms at multiple locations on the ligand.
13. Dock or Minimize a ligand inside a ligand binding pocket.

14. Calculate docking score and strain.
15. Dock using tethers and distance restraints.
16. Dock allowing specific residues in the receptor to be flexible.
17. Display hydrogen bonds, binding pocket, unsatisfied hydrogen bonds, and atomic energy circles.
18. On-the-fly docking and scoring of replacement groups.
19. Fragment docking and 4D docking for induced fit.
20. Covalent docking and  Ligand-based docking to APF 3D pharmacophore

Find Best Replacement Group

You have the option to decide whether you want to screen the modifying groups that are integrated into ICM, or if you prefer, you can use your table of modifier groups. If you opt for your table, you will need to load the table (in sdf file format) into ICM and specify the table’s name in this dialogue box.

ICM will attach each fragment to the target atom, evaluate its energy, and then provide you with a ranked table based on the calculated scores

Multiple Position Group Scan:

This feature enables you to modify groups and heteroatoms at various positions within the ligand. This tool allows you to select individual hydrogens or select all the hydrogens and then the tool will substitute the selected hydrogens with the different R groups in each of the positions. So it’s a useful way to do scaffold hoping or to move away from a patented molecule. Once the substituted molecules are docked it will give us the RTCNN score and the LE ( Ligand Editor) score.

Core Replacement:

This function helps identify the most suitable scaffold replacement or linker fragment from a database of chemicals in either 3D or 2D format. You can choose two or more connection points or areas for replacement interactively and then search for potential fragments within the 3D database.

It is possible to utilize pharmacophoric and Atomic Property Fields (APF) characteristics to match and assess potential linkers based on their properties