Effect of graphene oxide on the conformational transitions of amyloid beta peptide: A molecular dynamics simulation study

• Multiple simulations showed that nanoscale graphene oxide (GO) and reduced graphene oxide (rGO) inhibited the toxic α-helix to β-sheet transitions of amyloid beta (Aβ) peptide.
• The adsorption of Aβ on GO was dominated by electrostatic interactions, whereas both van der Waals and electrostatic interactions contributed in the adsorption of Aβ on rGO.
• rGO was more effective in inhibiting the conformational transitions and dynamics of Aβ due to the increase in hydrophobic π regions as suggested by conformational entropy and secondary structure analysis.

The interactions between nanomaterials (NMs) and amyloid proteins are central to the nanotechnology-based diagnostics and therapy in neurodegenerative disorders such as Alzheimer's and Parkinson's. Graphene oxide (GO) and its derivatives have shown to modulate the aggregation pattern of disease causing amyloid beta (Aβ) peptide. However, the mechanism is still not well understood. Using molecular dynamics simulations, the effect of graphene oxide (GO) and reduced graphene oxide (rGO) having carbon:oxygen ratio of 4:1 and 10:1, respectively, on the conformational transitions (alpha-helix to beta-sheet) and the dynamics of the peptide was investigated. GO and rGO decreased the beta-strand propensity of amino acid residues in Aβ. The peptide displayed different modes of adsorption on GO and rGO. The adsorption on GO was dominated by electrostatic interactions, whereas on rGO, both van der Waals and electrostatic interactions contributed in the adsorption of the peptide. Our study revealed that the slight increase in the hydrophobic patches on rGO made it more effective inhibitor of conformational transitions in the peptide. Alpha helix-beta sheet transition in Aβ peptide could be one of the plausible mechanism by which graphene oxide may inhibit amyloid fibrillation.

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