Initially, the Protein Data Bank provided the three-dimensional structure of the amyloidbeta 40 type 2 filaments (PDB ID: 8qn6) , and approximately 8216 ligands were selected from the Zinc20 Database . The amyloid-beta 40 type 2 was deposited in the Protein Data Bank in September 2023, and based on our knowledge, this is the first time inhibitors against this particular form of amyloid protein have been developed. LogP values were set to LogP = 2 to filter the ligands because these compounds have good oral and intestinal absorption. The filtered ligands were eventually obtained in pdbqt file format. The interaction positions of the ligands to the protein were then determined by employing the AutoDock Vina 1.5.6 software . The PLIP assessed the protein-ligand binding after using the AutoDock scoring method to determine the top five candidates for the most vital binding reactions . We have also simulated the fibril on the plasma membrane's surface to understand its binding mechanism and ligand binding mechanism. First, the CHARMM-GUI webserver was used to design the plasma membrane using the following configurations: DOPC 40%, DOPE 15%, DOPS 10%, Cholesterol 20%, and Sphingomyelin (DSM) 15%. In the next step, the fibril was docked on the plasma membrane's surface. Finally, we used the YASARA program to simulate the fibril-membrane interactions , and the amber ff14sb force field was used as it is among the best for protein interactions. To account for the interference of water molecules, they were placed in the simulation box using the TIP3P water model . Sodium (Na+) and Chloride (Cl-) ions were added to the system to mimic the physiological or realistic conditions. Two main precautions were taken to prepare for the simulation: minimization (the positions of atoms were adjusted to avoid unfavorable interactions) and equilibration (the following minimization, the system is left to reach a stable state). After the preparation, the MD production run was carried out and observed to study the dynamics of interactions between the fibril and the membrane. Cluster analysis was then used to group similar structures for analysis, and the PRODIGY program assessed the binding energies between fibrils and ligands .