Poster abstracts

Poster number 18 submitted by Lipika Baidya

Bridging of Ions Induces Structural Switch in the Conformational Ensemble of Poly(ADP-Ribose) (PAR)

Lipika Baidya (Department of Chemistry, State University of New York, Buffalo, NY, USA - 14260), Hung T Nguyen (Department of Chemistry, State University of New York, Buffalo, NY, USA - 14260)

Abstract:
Poly adenosine diphosphate ribose (PAR) is a highly charged, intrinsically flexible nucleic-acid-like homopolymer made up of adenosine diphosphate ribose (ADP-ribose) units. Despite its lack of stable secondary or tertiary structure, PAR plays a critical role in regulating key biological processes such as DNA repair, chromatin remodeling, and programmed cell death via liquid-liquid phase separation. Abnormal accumulation of PAR has been linked to neurodegenerative diseases. To understand how PAR carries out these functions, it's essential to explore its structural and dynamic properties. However, due to its inherent flexibility, experimental data on PAR are scarce. Atomistic simulations, which are typically used to study the detailed microscopic behavior of biomolecules, are limited in their ability to model PAR due to the absence of an appropriate force field. To address this, we developed a five-bead coarse-grained model for PAR, where each phosphate, sugar, and base group is represented by a distinct bead. We compared the structural properties of PAR with those of homopolymeric RNA (polyU and polyA), which share similar backbone charge densities and composition, at various ion concentrations (Na+, Mg2+, Ca2+). Our results suggest that PAR undergoes a more pronounced structural transition compared to RNA in the presence of divalent ions (Mg2+, Ca2+), likely due to preferential ion binding. Furthermore, we observed that ions bridge phosphate groups between consecutive nucleotides in PAR more effectively than in RNA, which drives the cooperative transition. Interestingly, the ion binding modes for PAR differ significantly from those in RNA. This work provides insight into how ions can induce structural transitions in PAR and their potential role in phase separation at DNA damage repair sites.

Keywords: poly(ADP-ribose) (PAR), Ion atmosphere, Molecular dynamics simulation