Early structural tendencies differ among amyloid beta 14 to 23 hexamers with F20P and E22A D23A substitutions

Abstract Short amyloid-β fragments provide controlled systems for examining how local sequence chemistry influences early structural behavior. For each sequence, we analyzed three 100-ns velocity-replicate all-atom molecular dynamics trajectories for six-peptide Aβ(14–23) systems of wild type (WT), F20P, and E22A–D23A. During 80–100 ns, DSSP β-content was 0.284 ± 0.012 for WT, 0.083 ± 0.020 for F20P, and 0.166 ± 0.007 for E22A–D23A (mean ± SEM across trajectory-level means). Complete md.xtc files were available for all nine replicates. Under an operational graph definition in which chains were linked by at least one interchain Cα contact ≤ 0.80 nm, the audited fractions of late-window frames with all six chains connected were 0.869 ± 0.131, 0.685 ± 0.315, and 0.999 ± 0.001, respectively. The F20P mean concealed pronounced replicate dependence, including one trajectory with only 5.4% fully connected frames. Mean interpeptide backbone hydrogen-bond counts were 13.45 ± 1.23 for WT, 9.21 ± 1.14 for F20P, and 10.42 ± 1.06 for E22A–D23A; after normalization by available backbone donor atoms, the values were 0.224 ± 0.021, 0.171 ± 0.021, and 0.174 ± 0.018. Full-system ion-coordinate reanalysis further showed system-dependent local Na + and Cl− distributions without establishing an ion-specific causal mechanism. These results describe starting-structure-dependent early tendencies rather than equilibrium oligomerization or fibril formation. Independent packing replicates, second-force-field validation, longer sampling, and experimental measurements remain necessary.