DS-ProGen: A Dual-Structure Deep Language Model for Functional Protein Design

Inverse Protein Folding (IPF) is a critical subtask in the field of protein design, aiming to engineer amino acid sequences capable of folding correctly into a specified three-dimensional (3D) conformation. Although substantial progress has been achieved in recent years, existing methods generally rely on either backbone coordinates or molecular surface features alone, which restricts their ability to fully capture the complex chemical and geometric constraints necessary for precise sequence prediction. To address this limitation, we present DS-ProGen, a dual-structure deep language model for functional protein design, which integrates both backbone geometry and surface-level representations. By incorporating backbone coordinates as well as surface chemical and geometric descriptors into a next-amino-acid prediction paradigm, DS-ProGen is able to generate functionally relevant and structurally stable sequences while satisfying both global and local conformational constraints. On the PRIDE dataset, DS-ProGen attains the current state-of-the-art recovery rate of 61.47%, demonstrating the synergistic advantage of multi-modal structural encoding in protein design. Furthermore, DS-ProGen excels in predicting interactions with a variety of biological partners, including ligands, ions, and RNA, confirming its robust functional retention capabilities.

Biological Sequence with Language Model Prompting: A Survey

Large Language models (LLMs) have emerged as powerful tools for addressing challenges across diverse domains. Notably, recent studies have demonstrated that large language models significantly enhance the efficiency of biomolecular analysis and synthesis, attracting widespread attention from academics and medicine. In this paper, we systematically investigate the application of prompt-based methods with LLMs to biological sequences, including DNA, RNA, proteins, and drug discovery tasks. Specifically, we focus on how prompt engineering enables LLMs to tackle domain-specific problems, such as promoter sequence prediction, protein structure modeling, and drug-target binding affinity prediction, often with limited labeled data. Furthermore, our discussion highlights the transformative potential of prompting in bioinformatics while addressing key challenges such as data scarcity, multimodal fusion, and computational resource limitations. Our aim is for this paper to function both as a foundational primer for newcomers and a catalyst for continued innovation within this dynamic field of study.