Ensemble docking model for the identification of PI3Kδ ligand

Human PI3K inhibition is well known and characterized in the literature. PI3K inhibitor can be classified into three general classes according to their binding mode in the ATP active site: Inhibitors that adopt a propeller-shaped or distorter propeller-shaped conformation are mostly PI3Kδ selective and those with flat conformation are pan-selective. We choose the six available crystallographic structure of PI3Kδ available in the PDB with all three conformations of PI3K inhibitors. RMSD between the structures were calculated and we observed a difference of 0.25 to 0.87 between them. An ensemble docking model was created and validated. All the structure was redocked with the GOLD program given an adequate RMSD value with ChemPLP function. The model is able to recognized ligand with flat, propeller-shaped or distorter propeller-shaped conformation in the ATP binding site. This model is a valuable tool to identify ligand that can be possible selective PI3Kδ inhibitors.