Prion diseases are fatal neurodegenerative diseases thought to arise from the post-translational conversionof normal cellular prion protein to a scrapie isoform. Experimental data suggest a role for copper(II) ionsin the process. An ab initio QM/MM approach and available experimental data were combined in order toidentify and evaluate three potential copper(II) ion binding sites in the C-terminal portion of the normalcellular prion protein. Our results suggest that copper(II) ion binds to His 187 but not to His 140 and His177 of the binding site in the cellular prion protein.