Molecular Insight into Amyloid Fibril-Templated Aggregation of Biomarkers.

ABSTRACT: The aggregation of misfolded proteins into β-sheet-rich fibrils constitutes a characteristic feature of neurodegenerative disorders and represents a therapeutic target. While cryo-electron microscopy has elucidated ordered binding patterns of small molecules on fibril surfaces, the mechanisms of ordered aggregate formation generally remain unclear. This study employs molecular dynamics (MD) simulations of the model ligand GTP-1 to examine fibril-templated ligand aggregation and elucidate the molecular determinants governing the aggregation process. Our results showed that in aqueous solution, GTP-1 molecules form dynamic clusters without preferential configurations, whereas tau fibril surfaces induce organized aggregation through protein-ligand hydrogen bonding and ligand-ligand π-π stacki

SUBMITTER: Zou R 

PROVIDER: S-EPMC12142574 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature