Ab initio simulations of Cu binding sites in the N-terminal region of PrPs
2006
The prion protein (PrP) binds Cu2+ ions in the octarepeat domain of the N-terminal tail up to
full occupancy at pH=7.4. Recent experiments show that the HGGG octarepeat subdomain is
responsible for holding the metal bound in a square planar coordination. By using first principle
ab initio molecular dynamics simulations of the Car-Parrinello type, the Cu coordination mode
to the binding sites of the PrP octarepeat region is investigated. Simulations are carried out for a
number of structured binding sites. Results for the complexes Cu(HGGGW)+(wat), Cu(HGGG)
and the dimer [Cu(HGGG)]2 are presented. While the presence of a Trp residue and a H2O
molecule does not seem to affect the nature of the Cu coordination, high stability of the bond
between Cu and the amide Nitrogens of deprotonated Gly’s is confirmed in the case of the
Cu(HGGG) system. For the more interesting [Cu(HGGG)]2 dimer a dynamically entangled
arrangement of the two monomers, with intertwined N-Cu bonds, emerges. This observation is
consistent with the highly packed structure seen in experiments at full Cu occupancy.
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