Poster abstracts

Poster number 21 submitted by Yaqiang Wang

Rules of engagement: how small molecules bind RNA in the SPIRAL database

Yaqiang Wang (Biophysics Department, Medical College of Wisconsin)

Abstract:
RNA molecules are increasingly recognized as compelling therapeutic targets; however, rational drug design remains constrained by the dynamic nature of RNA structure and a scattered landscape of experimental data. Although advanced biophysical techniques have rapidly accelerated the determination of complex RNA structures, there is a critical need to systematically aggregate and analyze these findings to understand the underlying principles for ligand design.
To bridge the gap between biophysics and computational drug discovery, we developed SPIRAL (Structural Pockets and Interacting RNA-Associated Ligands), a curated database of RNA-small molecule structures from the PDB covering 1,137 ligand-binding events. SPIRAL addresses the field's informatics bottleneck by providing standardized datasets that map the physical and chemical features of RNA-small molecule interactions and RNA tertiary binding pockets. By extracting unified principles from diverse, experimentally determined complexes, SPIRAL provides a platform to evaluate how specific RNA topologies and motifs preferentially accommodate small molecules. To enable these comparisons, we also introduced the Composite Binding Quality Score (CBQS), a novel framework that quantifies interaction quality across the full structural diversity of the dataset.
I will introduce the CBQS framework and highlight the key insights derived from the dataset to demonstrate the driving forces behind RNA-ligand recognition. Finally, I will discuss how the community can leverage this resource to inform rational ligand design and accelerate the next generation of RNA-targeted therapeutics.

References:
Lu XJ, Wang Y. Structural Pockets and Interacting RNA-Associated Ligands (SPIRAL): A DSSR-enabled Meta-Analysis of RNA-Small Molecule Recognition. bioRxiv [Preprint]. 2026. doi: 10.64898/2026.05.19.726393. PMCID: PMC13228370.

Keywords: RNA Therapeutics, Structural biology, RNA small molecule interaction