(3.3) Final subpocket-based fragmentation. The original ligand is now fragmented only at bonds crossing two subpockets, while storing for each fragment the subpocket that it occupies. The subpockets of neighboring fragments are compared in order to detect unwanted subpocket connections (see section "(2) Subpocket definition and allowed connections"). (i) If a connection between subpockets FP and B1 or FP and B2 is detected, the distance of the FP fragment is calculated to the GA subpocket center. If this distance is smaller than 5 Å, this fragment is reassigned to GA instead (applied to only 15 cases). Else, the fragment in B1 or B2, respectively, is assigned to pool X. (ii) If any unwanted subpocket connection is still present after this procedure, the complete ligand is excluded from the fragment library (see Table (B.4) and "Results and Discussion: Subpocket connections" for more detail).