Prion diseases are fatal neurodegenerative diseases thought to arise from the post-translational conversion of normal cellular prion protein to a scrapie isoform. Experimental data suggest a role for copper(II) ions in the process. An ab initio QM/MM approach and available experimental data were combined in order to identify and evaluate three potential copper(II) ion binding sites in the C-terminal portion of the normal cellular prion protein. Our results suggest that copper(II) ion binds to His 187 but not to His 140 and His 177 of the binding site in the cellular prion protein.
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