Jul 2026· IEEE journal of biomedical and health informatics· Vol PP, pp. 1-16· 0 citations
Medicine
TL;DR
Evaluations on eight MoleculeNet datasets show that MSMPP significantly outperforms state-of-the-art models, demonstrating its effectiveness in integrating multi-view intra-molecular features, inter-molecular features and cross-task information.
Abstract
Molecular property prediction is a cornerstone for accelerating drug discovery, providing a computational way to alleviate the low success rate, high cost, and long development cycle of conventional pharmaceutical research and development. However, existing computational methods have obvious limitations: most current deep learning approaches rely on a single molecular view, failing to fully capture the multi-dimensional features of molecular structures; they mainly focus on intra-molecular features while ignoring inter molecular information and cross-task correlations; and limited labeled data severely impairs their generalization to novel molecules. To address these issues, we propose MSMPP, a multi-scale, multi-view fusion framework for molecular property prediction that learns intra- and inter scale features simultaneously. For intra-scale feature learning, MSMPP integrates TxGemma-enhanced 1D sequence representations, Graph Transformer-derived 2D topological graph features, and Uni-Mol-derived 3D molecular conformational features. The Graph Transformer models long-range atomic dependencies, while the two pretrained models provide task-agnostic molecular prior knowledge from large-scale pretraining corpora, thereby improving generalization to novel molecules. For inter-scale feature learning, MSMPP constructs an inter-molecular graph (IMG) that explicitly models global pairwise interactions among chemically similar molecules and also extracts the cross-task features. Evaluations on eight MoleculeNet datasets show that MSMPP significantly outperforms state-of-the-art models, demonstrating its effectiveness in integrating multi-view intra-molecular features, inter-molecular features and cross-task information. Overall, MSMPP provides a competitive tool for molecular property prediction and supports the acceleration of drug discovery workflows.
Molecular deep learning plays an important role in addressing challenging molecular property prediction tasks. However, labeled molecular data remain scarce, and the majority of existing studies predominantly employ single-modal methods. Most single-modal models face limitations in simultaneously capturing molecular topological features and modeling long-range dependencies in sequences. In this study, we propose a novel multimodal alignment framework for joint modeling of molecular graphs and sequences, called Mol-ME. The framework incorporates a data augmentation strategy to enhance model performance under limited labeling conditions. Mol-ME comprises four core modules. The first module consists of dual encoders that generate graph-based and sequence-based molecular representations, which are then aligned through contrastive learning. The second module, a gated cross-modal fusion network, enables fine-grained integration of these representations by leveraging both the cross-attention mechanism and the gating mechanism. The third module is a motif-aware feature extractor that captures latent relationships among molecular substructures. The final module employs ensemble learning to predict on extracted representations, which captures complex nonlinear relationships and compensates for the modeling limitations of single shallow networks. Experimental results on 9 benchmark data sets demonstrate that Mol-ME consistently outperforms all baseline methods, achieving new state-of-the-art (SOTA) performance in molecular property prediction.
Baoren Huang, Mu Chen, Junjie Luo et al.· Journal of Chemical Informat...· 0 citations
Molecular property prediction is a critical task in accelerating drug discovery. While deep learning has shown promise, prevailing single-modal methods struggle to integrate multi-source (e.g., atomic graph and molecular fingerprints), heterogeneous chemical knowledge, thereby failing to holistically represent molecular structures and capture the high-order synergistic interactions governing their functions. To address these challenges, we present HyperMolFusion, a hypergraph-enhanced multi-modal fusion model for molecular property prediction. Compared with traditional graphs limited to pairwise atomic bonds, HyperMolFusion models chemical motifs as hyperedges to explicitly capture high-order structural correlations and encode complex molecular interactions. The framework comprises three core representation learning modules: AtomConv for local atomic interaction learning via attention-enhanced message passing, HyperConv for motif-level high-order correlation extraction via hypergraph convolution with GRU gating, and a mixed molecular fingerprint module that adaptively integrates MACCS, PubChem, and Pharmacophore fingerprints. A chemically guided attention (CGA) mechanism then dynamically fuses these multi-level features into hierarchical molecular representations, alleviating over-smoothing and preserving structural information effectively. Evaluated on eight MoleculeNet benchmarks (covering regression and classification tasks), HyperMolFusion achieves promising performance. For regression, it achieves an RMSE of 0.611 in lipophilicity, 0.653 in ESOL, and 0.951 in FreeSolv. For classification, it achieves a ROC-AUC of 0.935 in ClinTox, 0.907 in BBBP, and 0.689 in SIDER. This work provides a systematic and effective solution for molecular property prediction: by holistically integrating atomic, motif, and global fingerprint information via hypergraph modeling, HyperMolFusion offers a more reliable computational tool to enhance the efficiency and accuracy of drug development pipelines.
Yawen Lin, Sheng Lian, Shaoxin Bian et al.· IEEE journal of biomedical a...· 0 citations
Predicting the toxicity of pharmaceutical compounds remains a major challenge in drug discovery. Early and accurate toxicity assessment is essential for eliminating harmful candidates before costly preclinical and clinical testing, thereby improving patient safety, reducing development costs, and accelerating the drug development process. Despite advances in computational toxicology, existing methods often struggle to capture complex molecular characteristics and maintain robust performance under limited-data conditions. To address these challenges, we propose 3Br-MGD, a novel three-branch framework that integrates deep learning and meta-learning for molecular toxicity prediction. The architecture combines complementary molecular representations: FingerprintMLP encodes Morgan fingerprint descriptors, Graph Convolutional Networks (GCNs) capture structural information from molecular graphs, and one-dimensional Deep Convolutional Neural Networks (1D-CNNs) extract sequential features from SMILES strings. These embeddings are integrated within a Prototypical Network-based few-shot learning framework, enabling rapid adaptation to new prediction tasks with limited labeled samples and improving generalization in low-resource settings. Experimental results on benchmark toxicity datasets demonstrate that 3Br-MGD consistently outperforms conventional baselines in predictive accuracy, robustness, and generalization. Furthermore, the integration of heterogeneous molecular encoders reduces dependence on large training datasets while enhancing interpretability through the exploitation of complementary chemical information from multiple molecular views.
A novel Dual-Attention Multimodal framework for Graphs and Sequence-based representations, so-called DAM-GS, which provides a promising solution for molecular property prediction with broad applications in drug discovery and computational molecular science.
Bay Van Nguyen, Vinh Truong, Ha Duong Thi Hong et al.· Journal of Chemical Informat...· 0 citations
This review provides a systematic overview of recent advances in SSL-based molecular property prediction and analyzes how multimodal molecular representation learning by integrating sequence, graph, three-dimensional structure, and textual information can improve the quality and expressiveness of molecular representations.
Shuning Yang, Lei Deng· Journal of Chemical Informat...· 0 citations
Learning effective molecular representations is crucial for accurate property prediction in AI-aided drug discovery. However, most existing molecular pre-training methods are still primarily based on 2D topological graphs, limiting their ability to exploit 3D geometric information. Moreover, methods that do incorporate 3D geometry often do not distinguish between the roles of atom-centered and bond-centered representations. To address these limitations, we propose GDGraph, a geometryenhanced dual-view framework for molecular representation learning. GDGraph models molecular geometry from two complementary structural perspectives: an atom view for capturing global spatial dependencies and a bond view for modeling local geometric patterns. To support this dual-view design, we introduce a multi-scale geometric feature encoding scheme and a view-specific geometry-aware learning strategy, enabling each view to focus on the geometric dependencies it is best suited to capture. Extensive experiments demonstrate that GDGraph achieves strong and stable performance on molecular property prediction benchmarks, and effectively predicts geometrysensitive quantum chemical properties on the QM9 dataset.
Yu Liu, Jonathan D. Hirst, Jianfeng Ren et al.· Annual International Compute...· 0 citations