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Through evolution, nature has presented a set of remarkable protein materials, including elastins, silks, keratins and collagens with superior mechanical performances that play crucial roles in mechanobiology. However, going beyond natural…

Materials Science · Physics 2023-12-19 Bo Ni , David L. Kaplan , Markus J. Buehler

Engineering new molecules with desirable functions and properties has the potential to extend our ability to engineer proteins beyond what nature has so far evolved. Advances in the so-called "de novo" design problem have recently been…

Machine Learning · Computer Science 2023-10-17 Adam Winnifrith , Carlos Outeiral , Brian Hie

The de novo design of proteins refers to creating proteins with specific structures and functions that do not naturally exist. In recent years, the accumulation of high-quality protein structure and sequence data and technological…

Biomolecules · Quantitative Biology 2025-04-24 Yujie Qin , Ming He , Changyong Yu , Ming Ni , Xian Liu , Xiaochen Bo

Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai

Proteins power a vast array of functional processes in living cells. The capability to create new proteins with designed structures and functions would thus enable the engineering of cellular behavior and development of protein-based…

Biomolecules · Quantitative Biology 2023-06-08 Yeqing Lin , Mohammed AlQuraishi

Designing de novo proteins beyond those found in nature holds significant promise for advancements in both scientific and engineering applications. Current methodologies for protein design often rely on AI-based models, such as surrogate…

Soft Condensed Matter · Physics 2024-02-08 A. Ghafarollahi , M. J. Buehler

Generative modeling has become a central paradigm in protein research, extending machine learning beyond structure prediction toward sequence design, backbone generation, inverse folding, and biomolecular interaction modeling. However, the…

Machine Learning · Computer Science 2026-03-30 Senura Hansaja Wanasekara , Minh-Duong Nguyen , Xiaochen Liu , Nguyen H. Tran , Ken-Tye Yong

Protein design aims to compose amino-acid sequences that fold into stable three-dimensional structures while satisfying targeted functional properties. The field is increasingly shifting toward vibe protein design, where a single model is…

Deep generative models show promise for $\textit{de novo}$ protein design, yet reliably producing designs that are geometrically plausible, evolutionarily consistent, functionally relevant, and dynamically stable remains challenging. We…

Biomolecules · Quantitative Biology 2025-07-15 Tianyuan Zheng , Alessandro Rondina , Gos Micklem , Pietro Liò

Generative artificial intelligence models learn probability distributions from data and produce novel samples that capture the salient properties of their training sets. Proteins are particularly attractive for such approaches given their…

Biomolecules · Quantitative Biology 2026-02-27 Filippo Stocco , Michele Garibbo , Noelia Ferruz

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

Designing proteins de novo with tailored structural, physicochemical, and functional properties remains a grand challenge in biotechnology, medicine, and materials science, due to the vastness of sequence space and the complex coupling…

Artificial Intelligence · Computer Science 2025-12-01 Fiona Y. Wang , Di Sheng Lee , David L. Kaplan , Markus J. Buehler

We present SeedProteo, a diffusion-based model for de novo all-atom protein design. We demonstrate how to repurpose a cutting-edge folding architecture into a powerful generative design framework by effectively integrating self-conditioning…

Biomolecules · Quantitative Biology 2026-02-25 Wei Qu , Yiming Ma , Fei Ye , Chan Lu , Yi Zhou , Kexin Zhang , Lan Wang , Minrui Gui , Quanquan Gu

The design of novel protein sequences with targeted functionalities underpins a central theme in protein engineering, impacting diverse fields such as drug discovery and enzymatic engineering. However, navigating this vast combinatorial…

Biomolecules · Quantitative Biology 2024-02-19 Yiheng Zhu , Zitai Kong , Jialu Wu , Weize Liu , Yuqiang Han , Mingze Yin , Hongxia Xu , Chang-Yu Hsieh , Tingjun Hou

Protein design with desirable properties has been a significant challenge for many decades. Generative artificial intelligence is a promising approach and has achieved great success in various protein generation tasks. Notably, diffusion…

Proteins are macromolecules that mediate a significant fraction of the cellular processes that underlie life. An important task in bioengineering is designing proteins with specific 3D structures and chemical properties which enable…

Quantitative Methods · Quantitative Biology 2022-05-31 Namrata Anand , Tudor Achim

Protein design is a fundamental challenge in biotechnology, aiming to design novel sequences with specific functions within the vast space of possible proteins. Recent advances in deep generative models have enabled function-based protein…

Machine Learning · Computer Science 2025-10-15 Nuowei Liu , Jiahao Kuang , Yanting Liu , Tao Ji , Changzhi Sun , Man Lan , Yuanbin Wu

Adeno-associated viral (AAV) vectors are widely used delivery platforms in gene therapy, and the design of improved capsids is key to expanding their therapeutic potential. A central challenge in AAV bioengineering, as in protein design…

Innovations like protein diffusion have enabled significant progress in de novo protein design, which is a vital topic in life science. These methods typically depend on protein structure encoders to model residue backbone frames, where…

Computational Engineering, Finance, and Science · Computer Science 2023-10-19 Weian Mao , Muzhi Zhu , Zheng Sun , Shuaike Shen , Lin Yuanbo Wu , Hao Chen , Chunhua Shen

De novo functional protein design aims to generate protein sequences that realize specified biochemical functions without relying on evolutionary templates, enabling broad applications in biotechnology and medicine. Existing approaches…

Quantitative Methods · Quantitative Biology 2026-05-05 Xinrui Chen , Yizhen Luo , Siqi Fan , Zaiqing Nie
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