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GRASSP: RNA Language Model-Enhanced Graph Attention with Adaptive Gating for RNA-Small Molecule Binding Site Prediction.

Created on 23 Aug 2026

Authors

Thi Lan Nguyen, Nguyen Quoc Khanh Le

Published in

Bioinformatics (Oxford, England). Aug 22, 2026. Epub Aug 22, 2026.

Abstract

RNA-small molecule binding site prediction is crucial for targeted drug discovery. Sequence-based methods are efficient but often fail to capture structural dependencies between nucleotides, whereas structure-aware graph models can better represent spatial interactions but typically rely on complex structural annotations and multi-stage preprocessing pipelines. We therefore developed GRASSP, a streamlined hybrid deep learning framework that integrates pretrained RNA language model (LM) representations with adaptive graph refinement.
GRASSP leverages nucleotide embeddings and predicted secondary-structure features from a pretrained RNA LM to construct spatial RNA graphs, followed by a lightweight two-step graph attention refinement module with adaptive gating to capture local and contextual nucleotide dependencies. Across four benchmark datasets (TE18, HARIBOSS, TL12, and JL10), GRASSP generally outperformed state-of-the-art baselines, with improvements of up to 24.1% in AUC and 44.5% in MCC. Ablation analyses showed that pretrained RNA representations provided the dominant predictive contribution, while spatial graph refinement offered complementary but dataset-dependent benefits. These results demonstrate that GRASSP provides a competitive framework for integrating pretrained RNA representations with spatial structural context while reducing reliance on additional handcrafted structural annotations.
Code and datasets are publicly available at https://github.com/langiocn/GRASSP, with an archival snapshot available on Zenodo at https://doi.org/10.5281/zenodo.21888291.
Supplementary data are available at Bioinformatics online.

PMID:
42633564
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.

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