# Protein design and RNA design: Perspectives

**Authors:** Xi Chen, Xu Dai, Peilong Lu

PMC · DOI: 10.1002/qub2.70029 · Quantitative Biology · 2025-12-22

## TL;DR

Deep learning is revolutionizing the design of proteins and RNA, enabling the creation of new biomolecules with specific functions and structures for various applications.

## Contribution

The paper highlights recent advances in AI-driven protein and RNA design, emphasizing new capabilities and translational applications.

## Key findings

- Generative deep learning frameworks now enable accurate backbone generation and sequence–structure co-design in protein design.
- RNA design is advancing with improved 3D structure prediction and generative algorithms, though challenges remain in model generalization.
- Applications include therapeutic developments like immune cell engineering and thermostable antitoxins.

## Abstract

Advances in deep learning and generative modeling have transformed the landscape of protein and RNA design, enabling rapid and precise creation of novel biomolecules with tailored structures and functions. In protein design, generative deep learning frameworks now support backbone generation, sequence optimization, and joint sequence–structure co‐design with unprecedented accuracy. These approaches have facilitated broad applications ranging from cyclic peptide and non‐natural fold engineering to functional tool development, including small‐molecule sensing, catalytic center scaffolding, allosteric switching, intracellular logic circuits, and the targeting of intrinsically disordered proteins. Emerging therapeutic applications—such as immune cell engineering, G protein‐coupled receptor‐targeted miniproteins, receptor‐degrading binders, and thermostable antitoxins—demonstrate the translational potential of computational design. Parallel progress in RNA design, driven by enhanced 3D structure prediction models and generative algorithms, is expanding capabilities in aptamer engineering and RNA–protein complexes, despite ongoing challenges in model generalization and experimental validation. Together, these developments highlight a new era of AI‐driven molecular engineering, in which unified protein–RNA modeling, large‐scale sampling, and automated experimental pipelines will accelerate the creation of programmable biological systems and next‐generation therapeutics.

## Linked entities

- **Proteins:** GPCR (G protein coupled receptor)

## Full-text entities

- **Genes:** CXCR6 (C-X-C motif chemokine receptor 6) [NCBI Gene 10663] {aka BONZO, CD186, CDw186, STRL33, TYMSTR}

## Full text

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## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC12798782/full.md

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Source: https://tomesphere.com/paper/PMC12798782