(i) In 113 cases, FP-B2 connections were detected initially. Manual inspection revealed two different methodological drawbacks that could be resolved by the introduced rules: First, in some cases a fragment was assigned to FP because its centroid was slightly closer to FP than GA, although visual inspection showed that the fragment acts as a gate from the front to the back cleft, and should therefore belong to GA (14 cases). The molecules containing these fragments could thus be included by reassigning them to GA (see "(3) Molecule fragmentation"). Second, the FP-B2 connection was observed when the FP fragment was relatively large. While part of it pointed mostly into the solvent, the part was still close enough to B2 and, thus, was assigned to this subpocket. Furthermore, very rare cases were manually observed where the fragment actually covered B2. Since the latter two cases could not be distinguished algorithmically, and the FP-B2 connection is rather unexpected, these B2 fragments were reassigned to pool X (99 cases). The same applies for FP-B1 connections,