The initial input file contains three components; (a) E3 ligase, (b) BRD4 protein, and (c) PROTAC. The E3-PROTAC-BRD4 protein was from Protein Data Bank (6BOY), a free database for large biological molecules . From this complex the PROTAC molecules were first retrieved and were mutated using the following steps: First, the PROTAC was converted to the mol2 file format. The PROTAC.mol2 file was then mutated to ten different PROTAC variants in SMILES format. The CReM (Chemically Reasonable Mutations) is a computational tool to perform chemical mutations of molecules to obtain 10 mutated PROTACs . In the next step, the mutated PROTACs were converted to PDB format to perform molecular docking simulations. The molecular docking was performed between E3-BRD4 complex and mutant PROTACs using the HDOCK2.4 software to obtain the E3-PROTAC-BRD4 complexes .