(ii) Connections between non-adjacent subpockets (e.g. SE-GA, AP-B1) usually occur when one of the two subpockets contains a large BRICS fragment (that cannot be further fragmented), which also spans the respective subpocket in between. This happened only rarely, i.e. for AP-B1 and AP-B2 connections in 4 and 3 cases, respectively. Note that potential SE-GA connections were not counted as these ligands do not contain an AP fragment and were excluded from the study beforehand.