Issue 7, 2020

Systematic analysis of the interactions driving small molecule–RNA recognition

Abstract

RNA molecules are becoming an important target class in drug discovery. However, the principles for designing RNA-binding small molecules are yet to be fully uncovered. In this study, we examined the Protein Data Bank (PDB) to highlight privileged interactions underlying small molecule–RNA recognition. By comparing this analysis with previously determined small molecule–protein interactions, we find that RNA recognition is driven mostly by stacking and hydrogen bonding interactions, while protein recognition is instead driven by hydrophobic effects. Furthermore, we analyze patterns of interactions to highlight potential strategies to tune RNA recognition, such as stacking and cation–π interactions that favor purine and guanine recognition, and note an unexpected paucity of backbone interactions, even for cationic ligands. Collectively, this work provides further understanding of RNA–small molecule interactions that may inform the design of small molecules targeting RNA.

Graphical abstract: Systematic analysis of the interactions driving small molecule–RNA recognition

Supplementary files

Article information

Article type
Research Article
Submitted
20 Мам. 2020
Accepted
20 Мам. 2020
First published
04 Мау. 2020

RSC Med. Chem., 2020,11, 802-813

Author version available

Systematic analysis of the interactions driving small molecule–RNA recognition

G. Padroni, N. N. Patwardhan, M. Schapira and A. E. Hargrove, RSC Med. Chem., 2020, 11, 802 DOI: 10.1039/D0MD00167H

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