Viet Thanh Duy Nguyen

Viet Thanh Duy Nguyen, John K. Johnstone, Truong-Son Hy

Proteins are inherently multiscale physical systems whose functional properties emerge from coordinated structural organization across multiple spatial resolutions, ranging from atomic interactions to global fold topology. However, existing protein representation learning methods typically operate at a single structural level or treat different sources of structural information as parallel modalities, without explicitly modeling their hierarchical relationships. We introduce PRIME (Protein Representation via Physics-Informed Multiscale Equivariant Hierarchies), a unified framework that models proteins as a nested family of five physically grounded structural graphs spanning surface, atomic, residue, secondary-structure, and protein levels. Adjacent levels are connected through deterministic, physics-informed assignment operators, enabling bidirectional information exchange via bottom-up aggregation and top-down contextual refinement. Experiments on standard protein representation learning benchmarks demonstrate strong and competitive performance across diverse tasks, with particularly notable gains on the Fold Classification benchmark, where PRIME outperforms the strongest geometric GNN baseline by margins of 13.80 and 18.30 points on the harder Superfamily and Fold splits, and achieves a state-of-the-art accuracy of 84.10% on Reaction Class prediction, surpassing all baseline methods, including ESM. Ablation studies confirm that each structural level contributes complementary and non-redundant information, and adaptive cross-attention analysis reveals that PRIME autonomously identifies the most task-relevant structural resolutions at prediction time. Our source code is publicly available at https://github.com/HySonLab/PRIME

Tien Dang, Viet Thanh Duy Nguyen, Minh Tuan Le et al.

Biomedical Knowledge Graphs (BKGs) integrate diverse datasets to elucidate complex relationships within the biomedical field. Effective link prediction on these graphs can uncover valuable connections, such as potential novel drug-disease relations. We introduce a novel multimodal approach that unifies embeddings from specialized Language Models (LMs) with Graph Contrastive Learning (GCL) to enhance intra-entity relationships while employing a Knowledge Graph Embedding (KGE) model to capture inter-entity relationships for effective link prediction. To address limitations in existing BKGs, we present PrimeKG++, an enriched knowledge graph incorporating multimodal data, including biological sequences and textual descriptions for each entity type. By combining semantic and relational information in a unified representation, our approach demonstrates strong generalizability, enabling accurate link predictions even for unseen nodes. Experimental results on PrimeKG++ and the DrugBank drug-target interaction dataset demonstrate the effectiveness and robustness of our method across diverse biomedical datasets. Our source code, pre-trained models, and data are publicly available at https://github.com/HySonLab/BioMedKG

Brijesh FNU, Viet Thanh Duy Nguyen, Ashima Sharma et al.

Dielectric materials are critical building blocks for modern electronics such as sensors, actuators, and transistors. With the rapid recent advance in soft and stretchable electronics for emerging human- and robot-interfacing applications, there is a surging need for high-performance dielectric elastomers. However, it remains a grand challenge to develop soft elastomers that simultaneously possess high dielectric constants (k, related to energy storage capacity) and low Young's moduli (E, related to mechanical flexibility). While some new elastomer designs have been reported in individual (mostly one-off) studies, almost no structured dataset is currently available for dielectric elastomers that systematically encompasses their molecular sequence, dielectric, and mechanical properties. Within this context, we curate a compact, high-quality dataset of acrylate-based dielectric elastomers, one of the most widely explored elastomer backbones due to its versatile chemistry and molecular design flexibility, by screening and aggregating experimental results from the literature over the past 10 years. Building on this dataset, we propose a multimodal learning framework that leverages large-scale pretrained polymer representations from graph- and sequence-based encoders. These pretrained embeddings transfer rich chemical and structural knowledge from vast polymer corpora, enabling accurate few-shot prediction of both dielectric and mechanical properties from molecular sequences. Our results represent a new paradigm for transferring knowledge from pretrained multimodal models to overcome severe data scarcity, which can be readily translated to other polymer backbones (e.g., silicones, urethanes) and thus accelerate data-efficient discovery of soft high-k dielectric elastomers. Our source code and dataset are publicly available at https://github.com/HySonLab/Polymers

Viet Thanh Duy Nguyen, Truong-Son Hy

Proteins are complex biomolecules that play a central role in various biological processes, making them critical targets for breakthroughs in molecular biology, medical research, and drug discovery. Deciphering their intricate, hierarchical structures, and diverse functions is essential for advancing our understanding of life at the molecular level. Protein Representation Learning (PRL) has emerged as a transformative approach, enabling the extraction of meaningful computational representations from protein data to address these challenges. In this paper, we provide a comprehensive review of PRL research, categorizing methodologies into five key areas: feature-based, sequence-based, structure-based, multimodal, and complex-based approaches. To support researchers in this rapidly evolving field, we introduce widely used databases for protein sequences, structures, and functions, which serve as essential resources for model development and evaluation. We also explore the diverse applications of these approaches in multiple domains, demonstrating their broad impact. Finally, we discuss pressing technical challenges and outline future directions to advance PRL, offering insights to inspire continued innovation in this foundational field.

Phuc Pham, Viet Thanh Duy Nguyen, Truong-Son Hy

Accurate identification of interactions between protein residues and ligand functional groups is essential to understand molecular recognition and guide rational drug design. Existing deep learning approaches for protein-ligand interpretability often rely on 3D structural input or use distance-based contact labels, limiting both their applicability and biological relevance. We introduce LINKER, the first sequence-based model to predict residue-functional group interactions in terms of biologically defined interaction types, using only protein sequences and the ligand SMILES as input. LINKER is trained with structure-supervised attention, where interaction labels are derived from 3D protein-ligand complexes via functional group-based motif extraction. By abstracting ligand structures into functional groups, the model focuses on chemically meaningful substructures while predicting interaction types rather than mere spatial proximity. Crucially, LINKER requires only sequence-level input at inference time, enabling large-scale application in settings where structural data is unavailable. Experiments on the LP-PDBBind benchmark demonstrate that structure-informed supervision over functional group abstractions yields interaction predictions closely aligned with ground-truth biochemical annotations.