Multimodal deep learning with a joint uncertainty quantification scheme for drug-target interaction prediction.

M²DDI: A Unified Framework for Dynamic Multimodal Fusion in Drug-Drug Interaction Prediction

Drug-drug interaction (DDI) event prediction is critical for ensuring patient safety and optimizing therapeutic outcomes. Existing computational approaches are limited by their inability to jointly model the heterogeneous mechanisms underlying DDIs, which span molecular structure, pharmacodynamic function, and network-mediated relations. To address this limitation, we introduce M2DDI, a unified framework for dynamic multimodal fusion in DDI prediction. M2DDI utilizes a Mixture-of-Experts architecture, with each expert dedicated to a distinct pharmacological modality. A novel prior-enhanced dual-path gating strategy adaptively selects relevant experts for each drug pair by integrating mechanism-matched feature queries and ATC-based biomedical priors, thereby aligning expert selection with underlying pharmacological mechanisms and addressing the challenge of data incompleteness. Empirical evaluation on benchmark datasets demonstrates that M2DDI achieves state-of-the-art performance, particularly in new drug scenarios. Additional robustness experiments show that M2DDI maintains high predictive accuracy even when modality-specific information is partially missing, outperforming existing methods under similar conditions. Analysis of expert selection patterns further confirms alignment with established pharmacological mechanisms. These results establish M2DDI as an effective and mechanism-aware solution for comprehensive DDI prediction. The code is available at: https://github.com/RunqingXuCn/M2DDI.

Deep cross-modal representation fusion learning for enhanced drug target affinity prediction.

Prediction of Drug Target Affinity (DTA) is essential for accelerating computational drug discovery and reducing experimental costs. However, traditional experimental approaches for DTA estimation are resource-intensive and are further challenged by the structural flexibility of both drugs and target proteins. In this work, we propose the PCBERT-GAT-DFFNN-DTA model, a three-stage deep cross-modal representation fusion framework for accurate DTA prediction. In the first stage, variable-length protein sequences are transformed into contextual representations using ProtBERT to obtain fixed-size protein embeddings. Drug molecules are represented using two modalities: sequence-based embeddings generated from ChemBERT and structure-based embeddings learned from molecular graphs using a Graph Attention Network (GAT). In the second stage, each modality is processed through dedicated subnetworks to refine features and reduce dimensionality while preserving modality-specific information. In the final stage, the refined representations are fused and passed to a Deep Feed-Forward Neural Network (DFFNN) to predict drug target binding affinity. The proposed model consistently outperformed most baseline methods under the S1-S3 evaluation settings across the benchmark datasets. Under the more challenging S4 blind setting, the model achieved strong performance on the KIBA dataset and competitive results on the Davis and Metz datasets. Compared with LLMDTA, the proposed approach achieves significant improvements in R2 scores across all datasets, demonstrating its effectiveness in learning complex drug protein interactions for reliable DTA prediction.

HFEDTI: A DTI Prediction Model Integrating Local–Global Feature Fusion and Weighted Ensemble Learning

Drug–target interaction (DTI) prediction is a critical step in drug discovery, and accurate prediction of potential interactions can significantly accelerate the drug-development process. Although deep-learning approaches have achieved promising performance in DTI prediction, two challenges remain: single models often fail to comprehensively capture heterogeneous sequence information, resulting in limited stability and generalization, while insufficient integration of local and global features restricts interaction representation. To address these limitations, we propose HFEDTI, a DTI prediction model that integrates hierarchical feature fusion and weighted ensemble learning. Specifically, a residual convolutional neural network (ResCNN) is employed to extract local structural features of drugs and targets, while a self-attention-based hierarchical bidirectional long short-term memory network (SAHBiLSTM) captures global contextual dependencies. Furthermore, a hierarchical heterogeneous attention mechanism is introduced to align and fuse multi-level cross-modal representations, and a weighted ensemble strategy based on validation performance ranking is developed to enhance model robustness and generalization. Experimental results on three benchmark datasets demonstrate the effectiveness of HFEDTI. On the DrugBank dataset, HFEDTI achieves an AUC of 0.9238 and an AUPR of 0.9327, improving the best-performing baseline by 0.90 and 1.40 percentage points, respectively. Moreover, HFEDTI consistently achieves strong performance on the C. elegans and Human datasets, further validating its effectiveness and generalization capability for DTI prediction.

Recent Advances in Deep Learning-Based Drug-Target Binding Affinity Prediction

It is indicated that although many methods report strong performance on standard benchmarks, their effectiveness is often influenced by dataset bias and limited evaluation settings, and most methods exhibit reduced performance in cold-start scenarios, highlighting challenges in generalization.

SCAD-DTA: spherical concept alignment with dynamic multi-modal fusion for drug-target affinity prediction.

MMU-DPI: Enhancing Generalization in Drug–Protein Interaction Prediction through Multimodal Learning and a Label Mix Strategy

Experimental results on multiple benchmark data sets demonstrate that MMU-DPI outperforms several state-of-the-art DPI prediction methods and indicate that MMU-DPI can serve as a useful computational tool for drug discovery.