We present a QM-derived empirical scoring function for the interaction between aromatic halogenated ligands and the carbonyl oxygen atom of the protein backbone. Applying this scoring function, we developed an algorithm that evaluates the potential of protein-bound ligands to form favorable halogen-bonding contacts upon scaffold decoration with chlorine, bromine, or iodine. Full recovery of all existing halogen bonds in the PDB involving the protein backbone was achieved with our protocol. Interestingly, the potential for introducing halogen bonds through scaffold decoration of unsubstituted aromatic carbon atoms appears to easily match the number of previously known halogen bonds. Our approach can thus be used as a blueprint for integration of halogen bonding into general empirical scoring functions, which at present ignore this interaction. Most importantly, we were able to identify a substantial number of protein-ligand complexes where the benefits and challenges of introducing a halogen bond by molecular design can be studied experimentally.