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Recent advances in protein backbone generation have achieved promising results under structural, functional, or physical constraints. However, existing methods lack the flexibility for precise topology control, limiting navigation of the…

Artificial Intelligence · Computer Science 2025-04-22 Zhengxi Lu , Shizhuo Cheng , Yuru Jiang , Yan Zhang , Min Zhang

Proteins are essential macromolecules defined by their amino acid sequences, which determine their three-dimensional structures and, consequently, their functions in all living organisms. Therefore, generative protein modeling necessitates…

Machine Learning · Computer Science 2024-10-18 Xinyou Wang , Zaixiang Zheng , Fei Ye , Dongyu Xue , Shujian Huang , Quanquan Gu

Protein sequence design has seen significant advances through discrete diffusion and autoregressive approaches, yet the potential of continuous diffusion remains underexplored. Here, we present DiMA, a latent diffusion framework that…

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…

Representation learning and \emph{de novo} generation of proteins are pivotal computational biology tasks. Whilst natural language processing (NLP) techniques have proven highly effective for protein sequence modelling, structure modelling…

Quantitative Methods · Quantitative Biology 2025-01-08 Benoit Gaujac , Jérémie Donà , Liviu Copoiu , Timothy Atkinson , Thomas Pierrot , Thomas D. Barrett

Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Previous works usually generate atoms in an auto-regressive way, where element types and 3D coordinates of atoms are generated one…

Biomolecules · Quantitative Biology 2024-07-16 Haitao Lin , Yufei Huang , Odin Zhang , Siqi Ma , Meng Liu , Xuanjing Li , Lirong Wu , Jishui Wang , Tingjun Hou , Stan Z. Li

Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

Structure-based drug design (SBDD) aims to design small-molecule ligands that bind with high affinity and specificity to pre-determined protein targets. Generative SBDD methods leverage structural data of drugs in complex with their protein…

Diffusion models have demonstrated strong potential in language modeling, offering various advantages over traditional autoregressive approaches. Their ability to generate and revise entire responses in parallel enables faster generation…

Machine Learning · Computer Science 2026-03-03 Michael Hersche , Samuel Moor-Smith , Thomas Hofmann , Abbas Rahimi

Developing effective representations of protein structures is essential for advancing protein science, particularly for protein generative modeling. Current approaches often grapple with the complexities of the SE(3) manifold, rely on…

Machine Learning · Computer Science 2025-10-14 Shaoning Li , Le Zhuo , Yusong Wang , Mingyu Li , Xinheng He , Fandi Wu , Hongsheng Li , Pheng-Ann Heng

Deep learning has been widely used for protein engineering. However, it is limited by the lack of sufficient experimental data to train an accurate model for predicting the functional fitness of high-order mutants. Here, we develop SESNet,…

Quantitative Methods · Quantitative Biology 2023-04-10 Mingchen Li , Liqi Kang , Yi Xiong , Yu Guang Wang , Guisheng Fan , Pan Tan , Liang Hong

Structure-based drug design (SBDD) is crucial for developing specific and effective therapeutics against protein targets but remains challenging due to complex protein-ligand interactions and vast chemical space. Although language models…

Biomolecules · Quantitative Biology 2024-08-20 Cong Fu , Xiner Li , Blake Olson , Heng Ji , Shuiwang Ji

Structure-based drug design (SBDD) leverages the three-dimensional geometry of proteins to identify potential drug candidates. Traditional approaches, rooted in physicochemical modeling and domain expertise, are often resource-intensive.…

Quantitative Methods · Quantitative Biology 2024-11-19 Zaixi Zhang , Jiaxian Yan , Yining Huang , Qi Liu , Enhong Chen , Mengdi Wang , Marinka Zitnik

Proteins play a critical role in carrying out biological functions, and their 3D structures are essential in determining their functions. Accurately predicting the conformation of protein side-chains given their backbones is important for…

Quantitative Methods · Quantitative Biology 2024-02-19 Yangtian Zhang , Zuobai Zhang , Bozitao Zhong , Sanchit Misra , Jian Tang

Proteins inherently possess a consistent sequence-structure duality. The abundance of protein sequence data, which can be readily represented as discrete tokens, has driven fruitful developments in protein language models (pLMs). A key…

Computational Engineering, Finance, and Science · Computer Science 2026-05-29 Yi Zhou , Haohao Qu , Yunqing Liu , Shanru Lin , Le Song , Wenqi Fan

The advent of deep learning has introduced efficient approaches for de novo protein sequence design, significantly improving success rates and reducing development costs compared to computational or experimental methods. However, existing…

Artificial Intelligence · Computer Science 2024-07-11 Yutong Hu , Yang Tan , Andi Han , Lirong Zheng , Liang Hong , Bingxin Zhou

Massive molecular simulations of drug-target proteins have been used as a tool to understand disease mechanism and develop therapeutics. This work focuses on learning a generative neural network on a structural ensemble of a drug-target…

Machine Learning · Computer Science 2022-05-24 N. Joseph Tatro , Payel Das , Pin-Yu Chen , Vijil Chenthamarakshan , Rongjie Lai

Unlocking the next generation of biotechnology and therapeutic innovation demands overcoming the inherent complexity and resource-intensity of conventional protein engineering methods. Recent GenAI-powered computational techniques often…

Nature creates diverse proteins through a 'divide and assembly' strategy. Inspired by this idea, we introduce ProteinWeaver, a two-stage framework for protein backbone design. Our method first generates individual protein domains and then…

Biomolecules · Quantitative Biology 2024-11-28 Yiming Ma , Fei Ye , Yi Zhou , Zaixiang Zheng , Dongyu Xue , Quanquan Gu

While Masked Diffusion Language Models (MDLMs) relying on token masking and unmasking have shown promise in language modeling, their computational efficiency and generation flexibility remain constrained by the masking paradigm. In this…

Computation and Language · Computer Science 2026-03-26 Fangyu Ding , Ding Ding , Sijin Chen , Kaibo Wang , Peng Xu , Zijin Feng , Haoli Bai , Kai Han , Youliang Yan , Binhang Yuan , Jiacheng Sun