We took one of the published BTK PTS (6W8I) as the reference structure for linker generation. To explore the effect of the linker length on the generation of PROTAC molecules, we imposed constraint on linker length which refers to the topological bond distance between POI warhead and E3 ligand. Given the published BTK PTSs, we set several cut-offs for linker length, i.e. linker length cut-off [7-9], [7-11], [7-13] and [7-15], and the definition of linker score can be seen in previous section.