After "local only" docking of DPC in the binding site of PTS, sometimes there is a large positional shift for the warheads of PROTACs comparing to the warheads of reference PROTAC. The larger the 𝑃 𝑠 value is, the more similar the warheads of PROTAC is to the reference. Here, ROCS was used to only calculate the shape similarity on site and no alignment optimization was done. For example in Figure , two PROTAC molecules process can be found in supporting materials. In current study, Bruton's tyrosine kinase (BTK) PROTAC was chosen as the test case. Published PTS crystal structure 6W8I was chosen as the reference structure for structure generation. For the diversity filter setting in the scoring function of RL, the 'IdenticalMurckoScaffold' option was used to increase the diversity of generated linkers. The "minscore" and "minsimilarity" paremeters were all set as 0.0, so that all generated PROTACs during RL run will be kept.