FIGURE 1.
Removing lysine side chain charges within the CLC in silico improved fibril stability. Starting with an energy-minimized model of a segment of PrPSc amyloid based on a parallel in-register β-sheet assembly of eight mouse PrP 90–231 molecules (Energy minimized) (32), molecular dynamic simulations were performed on either the wild-type octamer with positively charged CLC side chains (Charged) or an octamer in which the CLC side chain charges were neutralized in silico (Uncharged). CLC lysine residues 101, 104, 106, and 110 are depicted in blue, β-strands are in green, and the cysteines forming the native disulfide bond are in yellow. In the energy-minimized octamer of wild-type PrP, the CLC lysine residues were stacked in close intermolecular proximity (Energy minimized). After 106-ns molecular dynamic simulations, the N-proximal region containing the CLC was more disordered in the wild-type (Charged) octamer than in CLC-neutralized (Uncharged) octamer.