PROTAC-INVENT takes a pair of fragment (E3-ligand and warhead for POI) and a reference PTS as input, and returns generated linkers and the predicted binding conformations of the full PROTAC compounds in the binding site of reference PTS (as shown in Figure1). Two modules are integrated in PROTAC-INVENT. Firstly, a generative model is trained to produce chemically feasible linker SMILES strings, following by forming complete PROTAC molecules together with the specified warhead and E3-ligand. REINVENT was used as the core generative engine for linker design and it was previously developed as an efficient generative model for de novo structure design. RL was utilized to search chemical space for optimization of molecular properties; Secondly, a 3D structure-based workflow was implemented to generate docking conformations of PROTACs and provide scores accordingly. The 3D based scores were then utilized to drive the RL (as shown in Figure ).