Molecular dynamics simulations of Cu(II) and the PHGGGWGQ octapeptide.

The interaction between Cu2+ and the copper-binding octapeptide region in the human prion protein has been investigated by molecular dynamics simulations. In total four different nonbonded and bonded models were used in the study. Charge sets containing atomic partial charges were developed for these models. Out of the considered models, the bonded model performed physically in the most correct way. The simulations with the bonded model showed that the water molecules in the axial position are very labile. The tryptophan indole ring can remain in a stable position on top of the equatorial coordination plane of copper without water mediation. Strong aromatic interaction was observed between the imidazole and indole rings. The nonbonded models showed a tendency for water-mediated interaction between the copper ion and different carbonyl oxygen atoms. In the case of the bonded model, a carbonyl group could also interact directly with the copper ion in one of the apical position.