The conformations of the amyloid-$β$ (21–30) fragment can be described by three families in solution

Alzheimer’s disease has been linked to the self-assembly of the amyloid-$β$ protein of 40 and 42 residues. Although monomers are in equilibrium with higher-order species ranging from dimers to heptamers, structural knowledge of the monomeric amyloid-$β$ $(Aβ)$ peptides is an important issue. Recent experimental data have shown that the fragment (21–30) is protease-resistant within full-length $Aβ$ peptides and displays two structural families in solution. Because the details of the $Aβ21–30$ structures found using distinct force fields and protocols differ at various degrees from those of the NMR structures, we revisit the conformational space of this peptide using the activation-relaxation technique (ART nouveau) coupled with a coarse-grained force field (OPEP v.3.0). We find that although $Aβ21–30$ does not have a secondary structure, it dominantly populates three structural families, with a loop spanning residues Val24-Lys28. The first two families, which differ in the nature of the electrostatic interactions, satisfy the five interproton rotating frame nuclear Overhauser effect spectroscopy (ROESY) distances and superpose well onto the NMR structures. The third family, which cannot be seen by ROESY NMR experiments, displays a more open structure. This numeric study complements the experimental results by providing a much more detailed description of the dominant structures. Moreover, it provides further evidence of the capability of ART OPEP in providing a reliable conformational picture of peptides in solution.