R‑BIND: An Interactive Database for Exploring and Developing RNA-Targeted Chemical Probes

While
the opportunities available for targeting RNA with small
molecules have been widely appreciated, the challenges associated
with achieving specific RNA recognition in biological systems have
hindered progress and prevented many researchers from entering the
field. To facilitate the discovery of RNA-targeted chemical probes
and their subsequent applications, we curated the RNA-targeted BIoactive
ligaNd Database (R-BIND). This collection contains an array of information
on reported chemical probes that target non-rRNA and have biological
activity, and analysis has led to the discovery of RNA-privileged
properties. Herein, we developed an online platform to make this information
freely available to the community, offering search options, a suite
of tools for probe development, and an updated R-BIND data set with
detailed experimental information for each probe. We repeated the
previous cheminformatics analysis on the updated R-BIND list and found
that the distinguishing physicochemical, structural, and spatial properties
remained unchanged, despite an almost 50% increase in the database
size. Further, we developed several user-friendly tools, including
queries based on cheminformatic parameters, experimental details,
functional groups, and substructures. In addition, a nearest neighbor
algorithm can assess the similarity of user-uploaded molecules to
R-BIND ligands. These tools and resources can be used to design small
molecule libraries, optimize lead ligands, or select targets, probes,
assays, and control experiments. Chemical probes are critical to the
study and discovery of novel functions for RNA, and we expect this
resource to greatly assist researchers in exploring and developing
successful RNA-targeted probes.