Benzimidazole inhibitors of the protein kinase CHK2: Clarification of the binding mode by flexible side chain docking and protein-ligand crystallography

Unconstrained rigid docking, flexible side chain docking and protein crystal structure determinations reveal a water-mediated hinge binding mode for a series of benzimidazole ligands of the protein kinase CHK2. This binding mode is different from those previously postulated in the literature and may provide a useful approach to selective small molecule inhibitor design.