Insights Into Resveratrol as an Inhibitor Against Aβ1-42 Peptide Aggregation:
A Molecular Dynamics Simulation Study

Priyanka      Borah; Venkata Satish   Kumar   Mattaparthi

doi:10.2174/2212796817666221221151713

Abstract

Background: Resveratrol (RSV), a polyphenolic compound, is reported to have antiaggregation properties against Amyloid-beta peptides. It is, therefore, significant to understand the mechanism of inhibition of Aβ_1-42 peptide aggregation by the RSV at the molecular level. We have used Molecular docking along with Molecular dynamics (MD) simulation techniques to address the role of RSV in the inhibition of Aβ_1-42 peptide aggregation.

Objective: To understand the role of Resveratrol on the Aβ_1-42 peptide aggregation.

Methods: In this computational study, we have docked the RSV to Aβ_1-42 peptide using Molecular Docking software and then performed MD simulation for the Aβ_1-42 peptide monomer Aβ_1-42 peptide- RSV complex using the AMBER force field. From the analysis of MD trajectories, we obtained salient structural features and determined the Binding Free Energy(BFE) and Per-residue Energy Decomposition Analysis (PRED) using MM-PBSA/GBSA method.

Results: The secondary structure and the conformational analysis obtained from MD trajectories show that the binding of RSV with the Aβ_1-42 peptide monomer causes an increase in the helical content in the structure of the Aβ_1-42 peptide. The BFE and PRED results show a high binding affinity (GB_total=- 11.07 kcal mol^-1; PB_total= -1.82 kcal mol^-1) of RSV with Aβ_1-42 peptide. Also, we found the RSV to interact with crucial residues (Asp 23 and Lys 28) of the Aβ_1-42 peptide. These residues play a significant role in facilitating the formation of toxic amyloid oligomers and amyloid fibrils. The salt bridge interaction between these residues D23-K28 was found to be destabilized in the Aβ_1-42 peptide when it is complexed with RSV.

Conclusion: In summary, it can be concluded that Resveratrol greatly aids the prevention of Aβ_1-42 peptide aggregation. Therefore, it can be considered a possible drug candidate for therapeutic strategies for Alzheimer’s disease.

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DOI https://dx.doi.org/10.2174/2212796817666221221151713	Print ISSN 2212-7968
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