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 package for identifying, characterizing, and visualizing ligand-binding sites in RNA. fpocketR was optimized, through 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 use of fpocketR to analyze RNA-ligand interactions and novel pockets in small and large RNAs, to assess ensembles of RNA structure models, and to identify pockets in dynamic RNA systems. fpocketR performs best with RNA structures visualized at high (≤3.5 Å) resolution, but also provides useful information with lower resolution structures and computational models. fpocketR is a powerful, freely available tool for discovery and analysis of ligand-binding pockets in RNA molecules.