Struct2GO-Enhanced: Multimodal Graph Attention Improves Protein Function Prediction

Protein function prediction has advanced substantially with the integration of AlphaFold2 structural information, yet current models remain constrained by incomplete multimodal feature fusion and limited attention mechanisms for capturing structural-functional relationships. Here, we present an enhanced framework that overcomes these limitations through three innovations: (i) Graph-CBAM, the first adaptation of convolutional block attention to graph neural networks for fine-grained structural feature extraction; (ii) complete multimodal fusion of Node2vec structural embeddings with amino acid one-hot encodings; and (iii) a dual-head self-attention pooling module that stabilizes node importance estimation. Extensive experiments on human protein data sets demonstrate that our model consistently outperforms existing benchmarks across all Gene Ontology branches. We report pronounced improvements, including an increase in Fmax by 2.9% on the Biological Process (BP) branch (0.481 to 0.495) and an enhancement of AUPR by 3.9% on the Cellular Component (CC) branch (0.763 to 0.793). Performance for Molecular Function (MF) remains competitive. Ablation analyses further confirm the independent contributions of structural embeddings, one-hot encodings, and Graph-CBAM. Overall, this work provides a more complete and practical solution for AlphaFold2-based protein function prediction, with particular advantages in predicting functions of proteins lacking protein-protein interaction data.

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Publication Details

Journal
Journal of Chemical Information and Modeling
Published
2026-01-02
DOI
https://doi.org/10.1021/acs.jcim.5c02419
Primary Topic
Bioinformatics and Genomic Networks
Type
article
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article

Struct2GO-Enhanced: Multimodal Graph Attention Improves Protein Function Prediction

Matthew Chin Heng Chua, Thanh Hoa Vo, Nguyen Quoc Khanh Le, Zihan Shi
Journal of Chemical Information and Modeling
Bioinformatics and Genomic Networks
article

Struct2GO-Enhanced: Multimodal Graph Attention Improves Protein Function Prediction

Matthew Chin Heng Chua, Thanh Hoa Vo, Nguyen Quoc Khanh Le, Zihan Shi
article en

Abstract

Protein function prediction has advanced substantially with the integration of AlphaFold2 structural information, yet current models remain constrained by incomplete multimodal feature fusion and limited attention mechanisms for capturing structural-functional relationships. Here, we present an enhanced framework that overcomes these limitations through three innovations: (i) Graph-CBAM, the first adaptation of convolutional block attention to graph neural networks for fine-grained structural feature extraction; (ii) complete multimodal fusion of Node2vec structural embeddings with amino acid one-hot encodings; and (iii) a dual-head self-attention pooling module that stabilizes node importance estimation. Extensive experiments on human protein data sets demonstrate that our model consistently outperforms existing benchmarks across all Gene Ontology branches. We report pronounced improvements, including an increase in Fmax by 2.9% on the Biological Process (BP) branch (0.481 to 0.495) and an enhancement of AUPR by 3.9% on the Cellular Component (CC) branch (0.763 to 0.793). Performance for Molecular Function (MF) remains competitive. Ablation analyses further confirm the independent contributions of structural embeddings, one-hot encodings, and Graph-CBAM. Overall, this work provides a more complete and practical solution for AlphaFold2-based protein function prediction, with particular advantages in predicting functions of proteins lacking protein-protein interaction data.

Journal of Chemical Information and ModelingVol. 66(2)
Yong In University (KR), National University of Singapore (SG), Taipei Medical University Hospital (TW), Abiomed (United States) (US), Pharmaceutical Biotechnology (Czechia) (CZ), Artificial Intelligence in Medicine (Canada) (CA), South East Technological University (IE), Taipei Medical University (TW)
Openalex Percentile: Top 99%
Bioinformatics and Genomic Networks
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Struct2GO-Enhanced: Multimodal Graph Attention Improves Protein Function Prediction — Matthew Chin Heng Chua, Thanh Hoa Vo, et al. · Journal of Chemical Information and Modeling (2026) | TGRS Research Map | TGRS