Elucidation of the Molecular Interaction Network Underlying Full-Length FUS Conformational Transitions and Its Phase Separation Using Atomistic Simulations.

ABSTRACT: Fused in Sarcoma (FUS) is a multidomain nucleic acid binding protein which orchestrates cellular functions such as gene expression, transcription, and DNA repair through liquid-liquid phase separation (LLPS). While crucial to understanding cellular processes, an atomic-level view of the molecular-level interactions associated with full-length (FL) FUS LLPS remains challenging due to its low solubility in vitro. Here, using all-atom (AA) molecular dynamics (MD) simulations, we examined the conformational dynamics and interactions of FL FUS in both dilute and condensed phases. Comparing two modern force fields (FFs)─Amber ff03ws and ff99SBws-STQ, we found that monomer simulation ensembles generated by both FFs exhibited qualitatively similar intramolecular interaction profiles dominat

SUBMITTER: Weng SL 

PROVIDER: S-EPMC12415842 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature