## 2 Results
### Structural Interaction and Docking  
In order to investigate the potential interaction of NA-17 LVFF [20] and NA-16 KLVF [19] with amyloid-beta monomer and fibrils, we utilized Flexible Alignment (Figure 4). Starting from our hypothesis, the purpose of this approach was to study the structural interaction of these molecules in order to break the formation of \(\beta\)-sheet conformations. In addition, by promoting the binding between NA-17 LVFF [20] and NA-16 KLVF [19] with amyloid-beta monomer, the probability to form fibrils and consequently \(\beta\)-sheet structures could decrease drastically (Figure 4a). Figure 4c,d shows different alignment patterns of our designed peptides and AB(1-42). Compared with Figure 1b, there are significant differences regarding amyloid-beta monomer conformation. These results suggest that our short peptide entangles to the primary sequence of AB(1-42), simultaneous with \(\alpha\)-helix motif inhibition. In this regard, the amyloid-beta changes its conformations to a random coil structure, which could increase the en  
Figure 4: (**a**) The proposed \(\beta\)-sheet breaker mechanism of fibril formation through peptide-based drug binding with AB(1-42) monomer. (**b**) The crystallographic structure of AB(1-42) monomer obtained from the Protein Data Bank and built with MOE software. The alignment pattern of AB(1-42) with (**c**) \({}^{17}\)LVFF [20]; (**d**) NA-17 LVFF [20]. The alignment pattern of AB(1-42) with (**e**) \({}^{16}\)KLVF [19] and (**f**) NA-16 KLVF [19]. tanglement process. Moreover, following addition of NA to the \({}^{17}\)LVFF [20] and \({}^{16}\)KLVF [19], a progression of \(\alpha\)-helix motif inhibition was noticed. Therefore, this may suggest that the peptide conjugates NA-\({}^{17}\)LVFF [20] and NA-\({}^{16}\)KLVF [19] could develop the entanglement process and hence may improve the process of the \(\beta\)-sheet breaker mechanism. Furthermore, in order to investigate the potential effect of these peptides for \(\beta\)-sheet breaker on the amyloid-beta fibrils, we utilized docking simulations. The docking results, according to the methodology described in Section 2.3, are presented in Figure 5. In addition, van der Waals interactions between \({}^{17}\)LVFF [20], NA-\({}^{17}\)LVFF [20], \({}^{16}\)KLVF [19] and NA-\({}^{16}\)KLVF [19] with A\(\beta_{(1-42)}\) fibrils are presented in Figure A1 and the structural interactions of the same systems in Figure A2. According to Figure 5, the molecular pathway through which peptides interact with A\(\beta_{(1-42)}\) fibrils seems to be at the top (Figure 5a-c) or at the bottom (Figure 5d) of the fibril. Interestingly, this suggests that if the interactions mainly occur at the end of the amyloid-beta fibril structure, there is no possibility of binding another A\(\beta_{(1-42)}\) monomer in order to increase the length of the fibril due to this particular blocking. Hence, the process of the \(\beta\)-sheet breaker could occur. Moreover, if in a therapeutic pathway a combination between \({}^{16}\)KLVF [19] and NA-\({}^{16}\)KLVF [19] is possible, where the first peptide could be attached at the top  
Figure 5: The docking simulation between A\(\beta_{(1-42)}\) fibrils (yellow \(\beta\)-sheet structures) and the proposed peptide-based drugs (black structures): (**a**) \({}^{17}\)LVFF [20] and (**b**) NA-\({}^{17}\)LVFF [20]; (**c**) \({}^{16}\)KLVF [19] and (**d**) NA-\({}^{16}\)KLVF [19]. (Figure 5c), and the peptide-based drug at the end of the fibril (Figure 5d) suggests that fibrillar formation obstruction could ensue. Furthermore, van der Waals interactions between \({}^{16}\)KLVF [19] and A\(\beta_{(1-42)}\) fibrils show that the peptide possesses the ability to reach the terminal core of the fibril structure by generating a pocket by reaching the oxygen-rich (carboxyl groups) and nitrogen-rich structures (amino groups), and therefore it could further destabilize it (Figure A1c). In addition, the other peptides seem to interact longitudinally with amyloid-beta (Figure A1a,b,d).