Computational Exploration of the Inhibitory Mechanism of mRNA against the Phase Separation of hnRNPA2 Low Complexity Domains DOI
Yuan Tan, Yujie Chen,

Tong Pan

и другие.

Journal of Chemical Information and Modeling, Год журнала: 2025, Номер unknown

Опубликована: Апрель 30, 2025

hnRNPA2, an RNA-binding protein involved in RNA metabolism and regulation, can undergo liquid-liquid phase separation (LLPS) to form dynamic biomolecular condensates. Previous experiments have reported that molecules inhibit the LLPS of hnRNPA2 low complexity domain (LCD). However, atomistic mechanisms underlying this inhibitory effect RNA-LCD interactions remain largely elusive. Herein, influence mRNA A2RE11 on single-chain conformational ensemble transient between LCD chains are investigated through all-atom-enhanced sampling molecular dynamics (MD) simulations. Our simulations reveal aromatic residues essential intrachain LCDs as well interchain dimers. Through binding positively charged LCD, undermines degree collapse disrupts stacking, hydrogen bonding, cation-π interactions. coarse-grained coexistence MD further underscore preeminence regulating behavior affinity for RGG Y/FG(G) motifs. These findings from multiscale lead a greater appreciation complex interaction network RNA-protein LCD.

Язык: Английский

Computational Exploration of the Inhibitory Mechanism of mRNA against the Phase Separation of hnRNPA2 Low Complexity Domains DOI
Yuan Tan, Yujie Chen,

Tong Pan

и другие.

Journal of Chemical Information and Modeling, Год журнала: 2025, Номер unknown

Опубликована: Апрель 30, 2025

hnRNPA2, an RNA-binding protein involved in RNA metabolism and regulation, can undergo liquid-liquid phase separation (LLPS) to form dynamic biomolecular condensates. Previous experiments have reported that molecules inhibit the LLPS of hnRNPA2 low complexity domain (LCD). However, atomistic mechanisms underlying this inhibitory effect RNA-LCD interactions remain largely elusive. Herein, influence mRNA A2RE11 on single-chain conformational ensemble transient between LCD chains are investigated through all-atom-enhanced sampling molecular dynamics (MD) simulations. Our simulations reveal aromatic residues essential intrachain LCDs as well interchain dimers. Through binding positively charged LCD, undermines degree collapse disrupts stacking, hydrogen bonding, cation-π interactions. coarse-grained coexistence MD further underscore preeminence regulating behavior affinity for RGG Y/FG(G) motifs. These findings from multiscale lead a greater appreciation complex interaction network RNA-protein LCD.

Язык: Английский

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