(2) Merge the linker of PROTAC with the warheads of reference ligand Once the alignment was done, the warheads of the generated PROTAC were removed and only the linker atoms were remained. The warheads of reference ligand were then copied and merged with the linker fragment of the generated PROTAC to form a re-combined PROTAC conformation (RPC). After this operation, the coordinates of warhead atoms in the RPC were exactly the same to that of reference ligand, but the bond lengths, dihedral angles between terminal atoms of the linker and warheads were not corrected yet and need to be fixed.