9Th Brazilian Symposium on Medicinal Chemistry

The aggregation of amyloid-β (Aβ) peptide in the brain is harmful in Alzheimer’s disease. Recently, Li1 shown that the cucurbiturils CB[7] and CB[8] inhibit the aggregation of the Aβ. However, the mechanism at atomistic level is not clear about this process. Herein, molecular dynamics (MD) simulation was used to study the CB[7]-Aβ interactions. Five initial configurations were built by positioned a CB[7] in different regions of a single chain of Aβ merged into a box contained 11,100 water molecules. The radius of gyration and RMSD values show that the CB[7]-Aβ complexes undergo significant conformational changes along the MD simulation. The lowest Gbinding were obtained when the Lys28 and Leu17 (N-terminal) are encapsulated on CB[7]. In conclusion, our results highlighted the inhibition of Aβ peptide aggregation by [CB7] in two ways: i) destabilizing the Aβ native structure, and ii) preventing the aggregation due steric effects along the encapsulation process of residues.