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Designing protein sequences that fold into a target 3-D structure, termed as the inverse folding problem, is central to protein engineering. However, it remains challenging due to the vast sequence space and the importance of local…

Quantitative Methods · Quantitative Biology 2026-03-17 Sazan Mahbub , Souvik Kundu , Eric P. Xing

Protein generative models have shown remarkable promise in protein design, yet their success rates remain constrained by reliance on curated sequence-structure datasets and by misalignment between supervised objectives and real design…

Machine Learning · Computer Science 2026-03-03 Ziwen Wang , Jiajun Fan , Ruihan Guo , Thao Nguyen , Heng Ji , Ge Liu

Structure-based protein design has attracted increasing interest, with numerous methods being introduced in recent years. However, a universally accepted method for evaluation has not been established, since the wet-lab validation can be…

Quantitative Methods · Quantitative Biology 2023-12-04 Chuanrui Wang , Bozitao Zhong , Zuobai Zhang , Narendra Chaudhary , Sanchit Misra , Jian Tang

Protein structures and functions are determined by a contiguous arrangement of amino acid sequences. Designing novel protein sequences and structures with desired geometry and functions is a complex task with large state spaces. Here we…

Chemical Physics · Physics 2022-09-01 Xeerak Agha , Nihang Fu , Jianjun Hu

Proteins are macromolecules that perform essential functions in all living organisms. Designing novel proteins with specific structures and desired functions has been a long-standing challenge in the field of bioengineering. Existing…

Biomolecules · Quantitative Biology 2023-03-03 Chence Shi , Chuanrui Wang , Jiarui Lu , Bozitao Zhong , Jian Tang

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a…

Biomolecules · Quantitative Biology 2023-11-27 Igor Melnyk , Aurelie Lozano , Payel Das , Vijil Chenthamarakshan

The recent breakthrough of AlphaFold3 in modeling complex biomolecular interactions, including those between proteins and ligands, nucleotides, or metal ions, creates new opportunities for protein design. In so-called inverse protein…

Biomolecules · Quantitative Biology 2025-07-22 Kai Yi , Kiarash Jamali , Sjors H. W. Scheres

Recently, diffusion- and flow-based generative models of protein structures have emerged as a powerful tool for de novo protein design. Here, we develop Proteina, a new large-scale flow-based protein backbone generator that utilizes…

Protein design often begins with the knowledge of a desired function from a motif which motif-scaffolding aims to construct a functional protein around. Recently, generative models have achieved breakthrough success in designing scaffolds…

Consistency and reliability are crucial for conducting AI research. Many famous research fields, such as object detection, have been compared and validated with solid benchmark frameworks. After AlphaFold2, the protein folding task has…

Biomolecules · Quantitative Biology 2023-08-01 Jaemyung Lee , Kyeongtak Han , Jaehoon Kim , Hasun Yu , Youhan Lee

Inverse protein folding is a fundamental task in computational protein design, which aims to design protein sequences that fold into the desired backbone structures. While the development of machine learning algorithms for this task has…

Machine Learning · Computer Science 2024-11-05 Yiheng Zhu , Jialu Wu , Qiuyi Li , Jiahuan Yan , Mingze Yin , Wei Wu , Mingyang Li , Jieping Ye , Zheng Wang , Jian Wu

A reduced model, which can fold both helix and sheet structures, is proposed to study the problem of protein folding. The goal of this model is to find an unbiased effective potential that has included the effects of water and at the same…

Soft Condensed Matter · Physics 2007-05-23 Nan-yow Chen

Improving the ability to predict protein function can potentially facilitate research in the fields of drug discovery and precision medicine. Technically, the properties of proteins are directly or indirectly reflected in their sequence and…

Biomolecules · Quantitative Biology 2024-11-19 Runze Ma , Chengxin He , Huiru Zheng , Xinye Wang , Haiying Wang , Yidan Zhang , Lei Duan

Protein structure prediction is pivotal for understanding the structure-function relationship of proteins, advancing biological research, and facilitating pharmaceutical development and experimental design. While deep learning methods and…

Machine Learning · Computer Science 2024-12-30 Kaihui Cheng , Ce Liu , Qingkun Su , Jun Wang , Liwei Zhang , Yining Tang , Yao Yao , Siyu Zhu , Yuan Qi

Designing novel functional proteins crucially depends on accurately modeling their fitness landscape. Given the limited availability of functional annotations from wet-lab experiments, previous methods have primarily relied on…

Machine Learning · Computer Science 2024-12-03 Zuobai Zhang , Pascal Notin , Yining Huang , Aurélie Lozano , Vijil Chenthamarakshan , Debora Marks , Payel Das , Jian Tang

Protein design has the potential to revolutionize biotechnology and medicine. While most efforts have focused on proteins with well-defined structures, increased recognition of the functional significance of intrinsically disordered…

Biomolecules · Quantitative Biology 2025-09-17 Giulio Tesei , Francesco Pesce , Kresten Lindorff-Larsen

The de novo design of ligand-binding proteins with tailored functions is essential for advancing biotechnology and molecular medicine, yet existing AI approaches are limited by scarce protein-ligand complex data. To circumvent this data…

Machine Learning · Computer Science 2026-03-03 Zhenqiao Song , Ramith Hettiarachchi , Chuan Li , Jianwen Xie , Lei Li

Computational design of protein-binding proteins is a fundamental capability with broad utility in biomedical research and biotechnology. Recent methods have made strides against some target proteins, but on-demand creation of high-affinity…

Proteins carry out biological functions through the coordinated action of groups of residues organized into structural arrangements. These arrangements, which we refer to as protein units, exist at an intermediate scale, being larger than…

Biomolecules · Quantitative Biology 2026-04-17 Gökçe Uludoğan , Buse Giledereli , Elif Ozkirimli , Arzucan Özgür

Recent advancements in machine learning techniques for protein folding motivate better results in its inverse problem -- protein design. In this work we introduce a new graph mimetic neural network, MimNet, and show that it is possible to…

Biomolecules · Quantitative Biology 2021-02-09 Moshe Eliasof , Tue Boesen , Eldad Haber , Chen Keasar , Eran Treister