COSMOsim3D is a unique and very robust method for automatic and unsupervised field-based ligand-ligand alignment and similarity searches. It utilizes local σ-profiles, which have been proved to contain the required information on the relevant molecular interactions.
The molecular surface charge approach of COSMOsim3D naturally enables scaffold hopping. Thus, the COSMOsim3D method is suited for datasets with different chemotypes, allowing users to find alternative chemical scaffolds with similar shape and polar features.
- • Pairwise alignment and similarity assessment: COSMOsim3D utilizes LSPs instead of chemical structure or pharmacophores to assess a molecule’s similarity to a template molecule. This enables scaffold hopping and allows users to deal with datasets of different chemotypes.
- • Multi-template alignment: It is possible to align multiple template molecules and use their superposition as a virtual template molecule. The virtual template molecule can be used for alignment and similarity assessment of potential ligand molecules.
- • Ligand-Based virtual screening: COSMOsim3D can be used to rank a set of potential ligand molecules according to their similarity to a single template or a virtual template stemming from the superposition of multiple ligands. Thus, it allows users to enrich ligand sets with potential cognate drugs, generating fewer false positives and more true hits.