Effects of anthocyanidins on the conformational transition of Aß(1-42) peptide: Insights from molecular docking and molecular dynamics simulations.
J Mol Graph Model
; 129: 108732, 2024 06.
Article
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| MEDLINE
| ID: mdl-38412813
ABSTRACT
Recent evidence from in vitro and in vivo studies has shown that anthocyanins and anthocyanidins can reduce and inhibit the amyloid beta (Aß) species, one of the hallmarks of Alzheimer's disease (AD). However, their inhibition mechanisms on Aß species at molecular details remain elusive. Therefore, in the present study, molecular modelling methods were employed to investigate their inhibitory mechanisms on Aß(1-42) peptide. The results highlighted that anthocyanidins effectively inhibited the conformational transitions of helices into beta-sheet (ß-sheet) conformation within Aß(1-42) peptide by two different mechanisms 1) the obstruction of two terminals from coming into contact due to the binding of anthocyanidins with residues of N- and second hydrophobic core (SHC)-C-terminals, and 2) the prevention of the folding process due to the binding of anthocyanidin with the central polar (Asp23 and Lys28) and native helix (Asp23, Lys28, and Leu34) residues. These new findings on the inhibition of ß-sheet formation by targeting both N- and SHC-C-terminals, and the long-established target, D23-K28 salt bridge residues, not with the conventional central hydrophobic core (CHC) as reported in the literature, might aid in designing more potent inhibitors for AD treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos beta-Amiloides
/
Enfermedad de Alzheimer
Límite:
Humans
Idioma:
En
Revista:
J Mol Graph Model
/
J. mol. graph. model
/
Journal of molecular graphics and modelling
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2024
Tipo del documento:
Article