SMARTFlexDB: a paired apo-holo RNA structure database and analysis platform for RNA conformational flexibility and small-molecule recognition

Abstract

RNA structures can undergo substantial conformational changes upon small-molecule binding, yet existing structural resources provide only static RNA-ligand snapshots without connecting ligand-bound (holo) RNA structures to corresponding ligand-free (apo) conformations. SMARTFlexDB is a curated database and analysis platform that uses paired apo-holo RNA structures to characterize conformational differences and RNA-small-molecule recognition. Candidate pairs were identified from the Protein Data Bank by matching RNA chains with at least 90% sequence identity and coverage, and fully conserved binding pocket nucleotides. The current release contains 434 binding pockets from 266 holo structures, linked to 186 apo structures to yield 1,187 pocket-level apo-holo pairs organized into 734 database entries, spanning 150 small molecules and 23 RNA functional classes. Each entry integrates RNA sequence and secondary-structure annotations, apo and holo three-dimensional structures, RNA-ligand atomic interactions, and quantitative descriptors of global and local conformational changes. An interactive web interface enables users to explore sequence alignments and structural overlays, compare secondary structures and RNA motifs, and upload paired apo-holo structures for customized analysis. By linking ligand-bound and ligand-free RNA structures, SMARTFlexDB provides a robust foundation for investigating RNA structural flexibility and supporting RNA-targeted small-molecule drug discovery. The database and analysis platform are available at https://aidd.rc.ufl.edu/app/smartflexdb/.