In a first step, inspired by the functional subpocket annotation in KLIFS, six functionally relevant subpockets were defined covering the ATP binding site. Note that KLIFS specifies eight subpockets, some of which describe relatively small subpockets that were combined into one subpocket in KinFragLib. Too small subpockets are algorithmically less desired in this case, because either too small fragments would be generated or larger fragments would span over several of these small subpockets. Additionally, a solvent-exposed pocket (SE) was introduced in KinFragLib, a region of the binding site occupied by many kinase inhibitors (see subpocket definitions in Table ).