Scaffold Replacement

Scaffold Replacement with SeeSAR and infiniSee

In some cases the replacement of the core moiety of the compound responsible for its biological activity, the so-called 'pharmacophore', may be necessary. This example explains how to start from a lead structure and synergistically combine SeeSAR and infiniSee to discover potential novel scaffolds. You can learn more about other methods of scaffold hopping here.

Goal: Discovering New Pharmacophores

Scaffold replacement aims to discover novel molecular structures which share similar chemical properties and functionalities with a lead molecule.
In this example we will use infiniSee to screen vast Chemical Spaces for related compounds and use SeeSAR to further assess our results for potential binding modes. Both steps can also be modified since synergies between two different methods enhance the success rate to find potential binders.

Continue this tutorial in SeeSAR/infiniSee and the step-by-step guide. Please use the attached PDB files.


Congratulations! You have discovered novel scaffolds through a combination of ligand-based and structure-based methods.
Other possibilities to perform scaffold replacement can be the application of pharmacophore constraints during docking, shape-focussed searches with the Similarity Scanner, or the use of ReCore in the Inspirator Mode.
It is always a good idea to use infiniSee to check which of your ideas can be easily realized or are commercially available to save time and resources. Simply drag-and-drop your compound from SeeSAR to infiniSee and start your search. By adjusting your search parameters you tell infiniSee what you consider important (e.g. chemical diversity of the results, obligatory molecular features) thus further enhancing your results.

Download SeeSAR and infiniSee and start your drug discovery project!