HARIBOSS: a curated database of RNA-small molecules structures to aid rational drug design

F. P. Panei (1, 2, 3) , R. Torchet (4) , H. Menager (4) , P. Gkeka (1) , M. Bonomi (2)

1 Sanofi Aventis R&D [Chilly-Mazarin]
2 Bioinformatique structurale - Structural Bioinformatics
3 ED515 - Ecole Doctorale Complexité du Vivant
4 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB

Motivation: RNA molecules are implicated in numerous fundamental biological processes and many human pathologies, such as cancer, neurodegenerative disorders, muscular diseases and bacterial infections. Modulating the mode of action of disease-implicated RNA molecules can lead to the discovery of new therapeutical agents and even address pathologies linked to ‘undruggable’ protein targets. This modulation can be achieved by direct targeting of RNA with small molecules. As of today, only a few RNA-targeting small molecules are used clinically. One of the main obstacles that have hampered the development of a rational drug design protocol to target RNA with small molecules is the lack of a comprehensive understanding of the molecular mechanisms at the basis of RNA-small molecule (RNA-SM) recognition. Results: Here, we present Harnessing RIBOnucleic acid—Small molecule Structures (HARIBOSS), a curated collection of RNA-SM structures determined by X-ray crystallography, nuclear magnetic resonance spectroscopy and cryo-electron microscopy. HARIBOSS facilitates the exploration of drug-like compounds known to bind RNA, the analysis of ligands and pockets properties and ultimately the development of in silico strategies to identify RNA-targeting small molecules.

Domaines: Bio-Informatique, Biologie Systémique [q-bio.QM]

F. P. Panei, R. Torchet, H. Menager, P. Gkeka, M. Bonomi. HARIBOSS: a curated database of RNA-small molecules structures to aid rational drug design. Bioinformatics, 2022, 38 (17), pp.4185-4193. ⟨10.1093/bioinformatics/btac483⟩. ⟨hal-03834209v2⟩