Employing CHEMBL Data with AAK1 and BIKE proteins to validate 3D-QSAR models

AAK1 (Adaptor Associated Kinase 1) and BMP2-K (BMP 2 inducible kinase) are serine threonine human kinases that have been shown to perform endocytosis and are associated with notch signalling pathways. Their inhibition forms the basis of potential drug targets. Using tools from Schrodinger Maestro, protein structures from PDB and molecules from Chembl were considered for investigation. The common core structure based on the 3-acylaminoindazole ring, found from the literature study, was used for clustering and ligand alignment docking. Docking poses generated were looked for having proton acceptor and donor bonds with the hinge region of the kinase protein. A QSAR (Quantitative Structure Activity Relationship) model was built for those ligands having good docking poses. Internal validation of Chembl compounds was grouped into a training and test set (80:20) for 3D- Field Based QSAR, providing a promising model for the external test set of molecules with unknown activities.