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A Comparative Study to Elucidate the Inhibitory Mechanism of a 6-Mer Fragment of Amyloid-Beta 42 Peptide as a Potential Therapeutic in Alzheimer’s Disease:Insights from Molecular Dynamics Simulations


Affiliations
1 Department of Molecular Biology and Biotechnology, Tezpur University, Sonitpur 784 028, India
 

Alzheimer’s disease is a neurodegenerative and incurable disease that is associated with the amyloid beta (Aβ) aggregation. We have carried out comparative molecular dynamics simulations of a 6-mer peptide and its analogues to elucidate the inhibitory mechanism on Aβ aggregation. The top analogue screened after refinement via docking exhibited significant inhibitory activities on both Aβ17–42 fibril as well as Aβ1–42 monomer, leading to disassembly of β-strands of Aβ1–42 peptide and fibril by interacting with C-terminal residues via hydrogen bonds and hydrophobic contacts. Binding of the analogue to the C-terminal region proves to be significant.

Keywords

Alzheimer’s Disease, Aggregation, Docking, Hydrophobic Interaction, Inhibitor Peptide.
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  • A Comparative Study to Elucidate the Inhibitory Mechanism of a 6-Mer Fragment of Amyloid-Beta 42 Peptide as a Potential Therapeutic in Alzheimer’s Disease:Insights from Molecular Dynamics Simulations

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Authors

Mary Dutta
Department of Molecular Biology and Biotechnology, Tezpur University, Sonitpur 784 028, India
Venkata Satish Kumar Mattaparthi
Department of Molecular Biology and Biotechnology, Tezpur University, Sonitpur 784 028, India

Abstract


Alzheimer’s disease is a neurodegenerative and incurable disease that is associated with the amyloid beta (Aβ) aggregation. We have carried out comparative molecular dynamics simulations of a 6-mer peptide and its analogues to elucidate the inhibitory mechanism on Aβ aggregation. The top analogue screened after refinement via docking exhibited significant inhibitory activities on both Aβ17–42 fibril as well as Aβ1–42 monomer, leading to disassembly of β-strands of Aβ1–42 peptide and fibril by interacting with C-terminal residues via hydrogen bonds and hydrophobic contacts. Binding of the analogue to the C-terminal region proves to be significant.

Keywords


Alzheimer’s Disease, Aggregation, Docking, Hydrophobic Interaction, Inhibitor Peptide.

References





DOI: https://doi.org/10.18520/cs%2Fv114%2Fi06%2F1207-1213