Xiaowen Ling, Zhiqiang Li, Yanbin Wang, Zhuhong You

As protein informatics advances rapidly, the demand for enhanced predictive accuracy, structural analysis, and functional understanding has intensified. Transformer models, as powerful deep learning architectures, have demonstrated unprecedented potential in addressing diverse challenges across protein research. However, a comprehensive review of Transformer applications in this field remains lacking. This paper bridges this gap by surveying over 100 studies, offering an in-depth analysis of practical implementations and research progress of Transformers in protein-related tasks. Our review systematically covers critical domains, including protein structure prediction, function prediction, protein-protein interaction analysis, functional annotation, and drug discovery/target identification. To contextualize these advancements across various protein domains, we adopt a domain-oriented classification system. We first introduce foundational concepts: the Transformer architecture and attention mechanisms, categorize Transformer variants tailored for protein science, and summarize essential protein knowledge. For each research domain, we outline its objectives and background, critically evaluate prior methods and their limitations, and highlight transformative contributions enabled by Transformer models. We also curate and summarize pivotal datasets and open-source code resources to facilitate reproducibility and benchmarking. Finally, we discuss persistent challenges in applying Transformers to protein informatics and propose future research directions. This review aims to provide a consolidated foundation for the synergistic integration of Transformer and protein informatics, fostering further innovation and expanded applications in the field.