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RNA-Ligand

Note

  • Autoregressive Approach:
    • Pocket2Mol, ICML, 2022
    • PocketFlow, Nature Mach. Intell., 2024
    • Lingo3DMol, Nature Mach. Intell., 2024
  • Diffusion Approach:
    • TargetDiff, ICLR, 2023
    • PMDM, Nature Commn., 2024
    • [Review] Diffusion Models for Molecules: A Survey of Methods and Tasks, 2025, arXiv:2502.09511

Drug RNA

RNA-ligand (small molecule) Interaction Prediction

Reviews

0. Protein-ligand prediction methods

  • 2024 Nature Machine Intelligence - Generic protein–ligand interaction scoring by integrating physical prior knowledge and data augmentation modelling
  • 2023 Nature machine intelligence - Calibrated geometric deep learning improves kinase–drug binding predictions
  • 2023 Nature machine intelligence - Learning characteristics of graph neural networks predicting protein–ligand affinities
  • 2023 Nature Machine Intell. - Interpretable bilinear attention network with domain adaptation improves drug–target prediction
  • 2022 Nature Biotech. - Prediction of protein–ligand binding affinity from sequencing data with interpretable machine learning
  • 2020 Cell - A Deep Learning Approach to Antibiotic Discovery

I. Known Examples & Experiments

  • ✅ Targeting miRNA precursor and mRNA’s UTR: Programming inactive RNA-binding small molecules into bioactive degraders, Nature 2023
  • ✅ Targeting lncRNA Xist with compounds that disrupt RNA structure and X inactivation, Nature 2022
  • 2021 Nature Biotech. - First small-molecule drug targeting RNA gains momentum
  • 2020 SLAS Discovery - Targeting RNA with Small Molecules: Identification of Selective, RNA-Binding Small Molecules Occupying Drug-Like Chemical Space
  • Targeting mRNA splicing (SMN2 exon7): A small molecule (SMN-C5) targeting RNA for a specific splicing correction of SMN2 exon7 to treat spinal muscular atrophy, Nature Chem. Biol. 2019
  • Targeting Ribo-switch: Selective small-molecule inhibition of an RNA structural element, Nature 2015
  • Targeting HIV TAR: Discovery of selective bioactive small molecules by targeting an RNA dynamic ensemble, Nature Chem. Biol. 2011

II. RNA element druggable by ligand

  • 2023 BIB - Structural interaction fingerprints and machine learning for predicting and explaining binding of small molecule ligands to RNA
  • 2022 BIB - RLBind: a deep learning method to predict RNA–ligand binding sites
  • 2021-Bioinformatics-Recognition of small molecule–RNA binding sites using RNA sequence and structure
  • 2019 Nature Chem. Biol. - Structural basis of a small molecule targeting RNA for a specific splicing correction
  • 2019 Methods in Enzymology Volume 623 - Differentiation and classification of RNA motifs using small molecule-based pattern recognition
  • 2018 Nature Chemical Biology - Small molecules that target group II introns are potent antifungal agents
  • [Riboswitch]
  • 2017 PNAS - Bioinformatic analysis of riboswitch structures uncovers variant classes with altered ligand specificity
  • 2014 PNAS - Functional conservation despite structural divergence in ligand-responsive RNA switches

III. RNA-ligand interaction prediction

  • ✅ 2023 Nature Machine Intell. - Large-scale chemical language representations capture molecular structure and properties
  • 2023 Nature Communications - Sequence-based drug design as a concept in computational drug design
  • ✅ [Drug RNA] 2020 NAR - Augmented base pairing networks encode RNA-small molecule binding preferences
  • [Graphical Modeling] 2021 Methods Mol Biol - Modeling and Predicting RNA Three-Dimensional Structures
  • 2015 WIREs Comput Mol Sci - Modeling of ribonucleic acid ligand interactions

IV. RIBOTAC

  • RIBOTAC (Ribonuclease Targeting Chimera) and PROTAC:
  • [review] PROTAC targeted protein degraders: the past is prologue, Nature Reviews Drug Discovery 2022
  • RIBOTAC & PROTAC 介绍