Enhanced identification of small molecules binding to hnRNPA1 via cryptic pockets mapping coupled with X-ray fragment screening.

ABSTRACT: The human heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is a prototypical RNA-binding protein essential for regulating a wide range of post-transcriptional events in cells. As a multifunctional protein with a key role in RNA metabolism, deregulation of its functions has been linked to neurodegenerative diseases, tumor aggressiveness, and chemoresistance, which has fuelled efforts to develop novel therapeutics that modulate its RNA-binding activities. Here, using a combination of molecular dynamics simulations and graph neural network pocket predictions, we showed that hnRNPA1 N-terminal RNA-binding domain (unwinding protein 1 [UP1]) contains several cryptic pockets capable of binding small molecules. To identify chemical entities for the development of potent drug candidates and exper

SUBMITTER: Dunnett L 

PROVIDER: S-EPMC11979464 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature