Molecular Dynamics Simulation Study of the Self-Assembly of Tau-Derived PHF6 and Its Inhibition by Oleuropein Aglycone from Extra Virgin Olive Oil.
J Phys Chem B
; 128(23): 5630-5641, 2024 Jun 13.
Article
em En
| MEDLINE
| ID: mdl-38814052
ABSTRACT
Alzheimer's disease (AD) and other taupathies are neurodegenerative disorders associated with the amyloid deposition of the Tau protein in the brain. This amyloid formation may be inhibited by small molecules, which is recognized as one of the best therapeutic strategies to stop the progression of the disease. This work focuses on the small nucleating segment, hexapeptide-paired helical filament 6 (PHF6), responsible for Tau aggregation. Using computational modeling and classical molecular dynamics simulations, we show that PHF6 monomers collapse in water to form ß-sheet rich structures, and the main olive oil polyphenol oleuropein aglycone (OleA) prevents peptide aggregation significantly. We gradually increase the ratio of the PHF6-OleA from 11 to 13 and find that for the 11 ratio, the peptide monomers are prone to form aggregated structures, while for the 12 ratio, the formation of the extended ß-sheet structure is significantly less. For a 13 ratio of protein/OleA, the peptide residues are sufficiently crowded by OleA molecules through hydrogen bonding, hydrophobic interactions, and π-π stacking; hence, the peptide chains prefer to exist in a monomeric random coil conformation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas tau
/
Simulação de Dinâmica Molecular
/
Azeite de Oliva
Limite:
Humans
Idioma:
En
Revista:
J Phys Chem B
Assunto da revista:
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia