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
de En
| 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Peptides bêta-amyloïdes
/
Maladie d'Alzheimer
Limites:
Humans
Langue:
En
Journal:
J Mol Graph Model
Sujet du journal:
BIOLOGIA MOLECULAR
Année:
2024
Type de document:
Article
Pays de publication:
États-Unis d'Amérique