The ICM Ligand Editor is a user-friendly graphical interface designed for optimizing ligands and facilitating drug design. This editor was developed in collaboration with medicinal chemists from Novartis, with a focus on ensuring both ease of use and precise ligand modeling.
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.
ICM Ligand editor offers various visualization options to the users. Users can visualize:
- Atomic Energy Circles
- Unsatisfied Hydrogen bond atom on Ligand
- Receptor surface colored by binding property
- Ligand Pocket surface
- H-Bond visualization
- Relaxed ligand in comparison with co-crystalized ligand.
Key feature of interactive 3D ligand editor
Some of the key features of the 3D ligand editor include:
- Interactively editing a ligand bound to a receptor
- Edit ligand in 2D or 3D and see the effect on ligand binding
- Change atom and bond types, switch stereo, cis and trans
- Delete atoms and bonds
- Rotate torsion angles
- Sample one or more substituents
- Screen a database of substituents to a specific atom of a ligand
- Save new ligands in a chemical spreadsheet, export to Excel, SDF, Mol or PDB format
- Convenient undo and redo modification feature
- Modification history table: Every ligand modification is stored and recorded in a chemical spreadsheet. Double-click on the spreadsheet to view the change.
- Hetero atom scan around ligand: This option allows you to scan groups and hetero atoms at multiple locations on the ligand.
- R-group scan around ligand: This option allows you to scan groups and hetero atoms at multiple locations on the ligand.
- Dock or Minimize a ligand inside a ligand binding pocket.
- Calculate docking score and strain.
- Dock using tethers and distance restraints.
- Dock allowing specific residues in the receptor to be flexible.
- Display hydrogen bonds, binding pocket, unsatisfied hydrogen bonds, and atomic energy circles.
- On-the-fly docking and scoring of replacement groups.
- Fragment docking and 4D docking for induced fit.
- 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.
In the field of drug design, bio isosteres play a crucial role in minimizing toxicity, modifying bioavailability, influencing metabolism, and adjusting the activity of the lead compound. Bio isosteres are essentially chemical substitutions with comparable chemical or physical characteristics that result in substantially similar biological properties when compared to another chemical compound.
Users can select the part they want to replace with a bioisostere and then select the suitable bioisostere database and scan the database. A Hitlist of suitable bioisostere replacements will be displayed and the user can rank them based on score.
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
1. Stiefl, N., Gedeck, P., Chin, D., Hunt, P., Lindvall, M., Spiegel, K., Springer, C., Biller, S., Buenemann, C., Kanazawa, T. and Kato, M., 2015. FOCUS Development of a Global Communication and Modeling Platform for Applied and Computational Medicinal Chemists. Journal of Chemical Information and Modeling, 55(4), pp.896-908.