fpocketR: A platform for identification and analysis of ligand-binding pockets in RNA

Abstract

Small molecules that bind specific sites in RNAs hold promise for altering RNA function, manipulating gene expression, and expanding the scope of druggable targets beyond proteins. Identifying binding sites in RNA that can engage ligands with good physicochemical properties remains a significant challenge. fpocketR is a software and framework for identifying, characterizing, and visualizing ligand-binding sites in RNA. fpocketR was optimized, through a comprehensive analysis of currently available RNA-ligand complexes, to identify pockets in RNAs able to bind small molecules possessing favorable properties, generally termed drug-like. Here, we demonstrate multiple, complex, uses of fpocketR to analyze RNA-ligand interactions and novel pockets in small and large RNAs, to assess ensembles of RNA structure models, to identify pockets in dynamic RNA systems, and to evaluate the shapes of RNA pockets. fpocketR performs best with RNA structures visualized at atomistic resolution but also provides useful information with lower resolution structures and computational models. fpocketR is a powerful, ligand-agnostic tool for discovery and analysis of targetable pockets in RNA molecules.