Fig. 6.

(A) Distribution of ${\chi }_{\mathit{fi}b}$ for A$\beta$40 (shown in red). The overlap parameter is computed with respect to the monomers in the experimental fibril structure. For A$\beta$40, the reference state is the monomer unit from the striated (U-bend) fibril structure (75) (Protein Data Bank [PDB] ID: 2M4J) (75). The shaded area under the curve, which corresponds to the $N^{*}$ state is in red. Inset shows an enlarged view of this section of the curve. (B) Distribution of ${\chi }_{\mathit{fi}b}$ for A$\beta$42 (shown in blue) using the monomer from the U-bend fibril structure (PDB ID: 2BEG) (71) as a reference. The shaded area under the curve (Inset) corresponds to the population of $N^{*}$ states with U-bend topology. (C) Same as B except that the overlap parameter, ${\chi }_{\mathit{fi}b}$, is calculated using the S-bend fibril structure (PDB ID: 2NAO) (44). The shaded area under the curve (Inset) corresponds to the population of $N^{*}$ states having S-bend topology. In A–C the purple curves correspond to $P\left({\chi }_{\mathit{fi}b}\right)$ computed from the restrained simulations (see SI Appendix for details) starting from the monomer present in the fibril structure. (A) A$\beta$40 fibril structure (PDB ID: 2M4J). (B) A$\beta 42$ U-bend fibril structure (PDB ID: 2BEG). (C) A$\beta$42 S-bend fibril structure (PDB ID: 2NAO). In all cases, the center of the distribution is approximately at ${\chi }_{\mathit{fi}b}$ = 0.28. This value corresponds to ${\chi }_c$ and is marked in the plots.