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Abstract
The prion protein, located mainly in neurons, is believed to play the role of metal ion transporter. A 32-residue region of the N-terminal domain, known as octarepeat, can bind up to four Cu ions. Different coordination modes have been observed and are strongly dependent on Cu concentration. Many theoretical studies carried out so far have focused on studying the coordination modes of a single copper ion. In this work we investigate the octarepeat region coordinated with four copper ions. Molecular dynamics (MD) and hybrid quantum mechanics/molecular mechanics (QM/MM) simulations using the polarizable AMOEBA force field have been carried out. Results indicate that the 4Cu-octarepeat complex forms a globular structure, in agreement with experimental results. Subsequent QM/MM simulations on several snapshots suggests the system is in a high-spin quintet state, with all Cu ions bearing one single electron, and all unpaired electrons are ferromagnetically
coupled.
Supplementary materials
Title
Structural and Electronic Analysis of the Octarepeat Region of Prion Protein with Four Cu(II) by Polarizable MD and QM/MM Simulations
Description
In the supplementary information we show the structures used for the parametrization, definitions of the studied models and some results from MD simulations such as radius of gyration, Cu-Cu distances and distances around each copper ion. k-means clustering analysis and some snapshots showing the interaction between tryptophan residues and metal centers are also provided. Finally we show some normal modes and non-covalent interaction and electron localization function plots.
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