Sharp-Focused Libraries - Joint Project Life Chemicals Inc. with Otava:

The receptor-based target-focused libraries are generated on the basis of computational estimation of compound interaction with 1 certain target of protein family (Sharp focusing). The core of these libraries design is flexible docking. After the docking, "rescoring" algorithm is applied.

The "rescoring" procedure includes correction of final summation of interaction energies (score) according to structural features of each ligand. At the final stage we scan each docking complex for H-bond(s) formed between ligand and critical (key) aminoacid residue(s) of the protein active site.

Detailed analysis of each protein-ligand complex obtained with docking allows design of unique focused libraries. The first seven sharp-focused libraries have been completed: 

• Human Fibroblast Growth Factor Receptor 1 Tyrosine Kinase (FGFR1K) focused library (1000 compounds)
• 3-Phosphoinositide-dependent kinase-1 (PDK-1) focused library (1000 compounds)
• cAMP dependent protein kinase (PKA ) focused library (1 100 compounds)
• Phosphatidylinositol 3-kinase (PI3K) focused library (1 400 compounds)
• Human Janus kinase 2 (JAK 2) focused library (1 300 compounds)
• Aurora B Kinase receptor-based focused library (2 144 compounds)
• Vascular endothelial growth factor receptor (VEGFR) kinase focused library (2 341 compounds)