Exploring the Impact of Curcumin and Carbon Nanotubes on BetaAmyloid Peptide Dimer: Insights from Molecular Dynamics Simulation and Density Functional Theory Methods.

Abstract

Aim: At the molecular level, the accumulation of beta-amyloid peptide is one of the important mechanisms in the formation of amyloid plaques. These plaques, in turn, are considered one of the important factors in the development of Alzheimer's disease. Therefore, it is important to study the factors affecting beta-amyloid peptides. This study aimed to investigate the impact of curcumin on the structure of beta-amyloid peptide dimers and how carbon nanotubes influence this interaction. The research focused on understanding the molecular dynamics and structural changes induced by curcumin to reduce beta-amyloid toxicity.

Background: Curcumin, a phenolic compound, is known for its ability to prevent the aggregation of beta-amyloid peptides, which are associated with neurodegenerative diseases. On the other hand, due to the hydrophobic nature of curcumin, its solubility in aqueous media is limited. To overcome this, a carrier is used. Carbon nanotubes are among the carriers of curcumin. Nanotubes are popular candidates for the delivery of effective pharmaceutical compounds due to their unique surface properties and biocompatibility. The use of a carrier affects the study of the mechanism of interaction of curcumin with the peptide, which in turn makes it difficult to study this mechanism. Thus, despite its recognized inhibitory action on beta-amyloid aggregation, there is limited understanding of its precise effects on the peptide's structure. This study addresses this gap by employing molecular dynamics simulations and density functional theory methods.

Objective: The objective of this study was to elucidate the structural effects of curcumin on betaamyloid peptide dimers and assess the modifying role of carbon nanotubes using computational methods.

Method: The effect of curcumin on beta-amyloid peptide dimers was studied using molecular dynamics simulations and density functional theory. The simulations were conducted both in the presence and absence of carbon nanotubes to assess their influence on curcumin's activity and the structural stability of the peptide.

Results: The presence of curcumin and carbon nanotubes induced relative instability in betaamyloid dimers. Curcumin exhibited stronger interactions with the N-terminal and C-terminal regions of the peptide than with the middle section. It also reduced the toxicity of the peptide by particularly affecting the salt bridge and the arrangement of Phe19, Ile31, and Leu34 residues. Carbon nanotubes mitigated curcumin's effects on the peptide, altering curcumin's behavior by reducing its activity, but increasing its solvation energy.

Conclusion: Curcumin plays a significant role in destabilizing beta-amyloid dimers and reducing their toxicity, with its effect being modulated by the presence of carbon nanotubes. This dual influence highlights the potential of using curcumin, alongside nanomaterials, in therapeutic strategies for neurodegenerative diseases. This study provided valuable insights into the molecular interactions among curcumin, beta-amyloid peptides, and carbon nanotubes. These findings can contribute to the development of more effective treatments targeting amyloid-related toxicity in neurodegenerative conditions.