BPS2026 – From structure to ion atmosphere to condensates: Divergent behavior of Poly(ADP-ribose) versus RNA

Poly(ADP-ribose) (PAR) is a highly charged, intrinsically flexible nucleic-acid-like homopolymer composed of ADP-ribose units. It serves as a critical post-translational modification that is rapidly synthesized in response to DNA damage, and participates in diverse important cellular processes, including DNA repair, chromatin remodeling, and RNA biogenesis, often through liquid-liquid phase separation (LLPS). However, PAR’s conformational heterogeneity and limited experimental or atomistic characterization have hindered our mechanistic understanding of these processes. To address this challenge, we developed a five-bead coarse-grained model of PAR and performed molecular dynamics simulations to compare its structural and phase behaviors with homopolymeric RNA (poly-rU and poly-rA) under varying ion environments (Na + , Mg 2+ , and Ca 2+ ). Our simulations reveal that PAR undergoes more pronounced structural transitions than RNA in the presence of divalent ions, driven by preferential ion binding and effective ion-mediated bridging of nearby phosphate groups. These interactions produce cooperative conformational changes and a distinctive ion atmosphere that differs markedly from that of RNA. Importantly, PAR exhibits a higher propensity for condensate formation than poly-rA in Mg 2+ , and the underlying mechanism of its phase transition differs from RNA-based LLPS. Our work provides a physically grounded model for PAR, uncovers unique behaviors that distinguish PAR from RNA, and offers mechanistic insights into PAR-driven biomolecular condensates.