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Protein sequence generation for engineering requires samples that are biophysically plausible and, when targeting a family/domain, remain recognizable members while exploring within-family diversity. Current discrete generative models…

Computational Engineering, Finance, and Science · Computer Science 2026-05-25 Langzhang Liang , Ming Yang , Yi Feng , Junfan Li , Shirui Pan , Yinghui Xu , Tianlei Ying , Yizhen Zheng , Zenglin Xu

The design of protein sequences with desired functionalities is a fundamental task in protein engineering. Deep generative methods, such as autoregressive models and diffusion models, have greatly accelerated the discovery of novel protein…

Machine Learning · Computer Science 2025-04-16 Zitai Kong , Yiheng Zhu , Yinlong Xu , Hanjing Zhou , Mingzhe Yin , Jialu Wu , Hongxia Xu , Chang-Yu Hsieh , Tingjun Hou , Jian Wu

Autoregressive generative models naturally generate variable-length sequences, while non-autoregressive models struggle, often imposing rigid, token-wise structures. We propose Edit Flows, a non-autoregressive model that overcomes these…

Machine Learning · Computer Science 2025-11-13 Marton Havasi , Brian Karrer , Itai Gat , Ricky T. Q. Chen

Proteins are shaped by gradual evolution under biophysical and functional constraints. Protein language models learn rich evolutionary constraints from large-scale sequences, and discrete diffusion-based protein language models~(\eg, DPLMs)…

Machine Learning · Computer Science 2026-05-14 Xinyou Wang , Liang Hong , Jiasheng Ye , Zaixiang Zheng , Yu Li , Shujian Huang , Quanquan Gu

The process of extracting valuable and novel insights from raw data involves a series of complex steps. In the realm of Automated Machine Learning (AutoML), a significant research focus is on automating aspects of this process, specifically…

Machine Learning · Computer Science 2024-02-06 Rafael Barbudo , Aurora Ramírez , José Raúl Romero

The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Generative modeling techniques such as Diffusion and Flow Matching have achieved significant successes in generating designable and diverse protein backbones. However, many current models are computationally expensive, requiring hundreds or…

Biomolecules · Quantitative Biology 2025-10-30 Junhua Chen , Simon Mathis , Charles Harris , Kieran Didi , Pietro Lio

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

Predicting protein properties is paramount for biological and medical advancements. Current protein engineering mutates on a typical protein, called the wild-type, to construct a family of homologous proteins and study their properties.…

Machine Learning · Computer Science 2024-06-26 Zhiqiang Zhong , Davide Mottin

Directed evolution is an iterative laboratory process of designing proteins with improved function by iteratively synthesizing new protein variants and evaluating their desired property with expensive and time-consuming biochemical…

Machine Learning · Computer Science 2025-09-08 Matouš Soldát , Jiří Kléma

Biological processes, functions, and properties are intricately linked to the ensemble of protein conformations, rather than being solely determined by a single stable conformation. In this study, we have developed P2DFlow, a generative…

Biological Physics · Physics 2025-03-05 Yaowei Jin , Qi Huang , Ziyang Song , Mingyue Zheng , Dan Teng , Qian Shi

Predicting the fitness impact of mutations is central to protein engineering but constrained by limited assays relative to the size of sequence space. Protein language models (pLMs) trained with masked language modeling (MLM) exhibit strong…

Machine Learning · Computer Science 2026-04-14 Jigang Fan , Xiaoran Jiao , Shengdong Lin , Zhanming Liang , Weian Mao , Chenchen Jing , Hao Chen , Chunhua Shen

Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…

Machine Learning · Computer Science 2025-10-01 Yogesh Verma , Markus Heinonen , Vikas Garg

While large language models (LLMs) excel at static scientific reasoning, they struggle to model the temporal structure of dynamic physical processes. We present EvoMD-LLM (Evolutionary Molecular Dynamics Large Language Model), a framework…

Artificial Intelligence · Computer Science 2026-05-29 Zhichen Tang , Zhengzheng Dang , Yulin Chen , Jixin Wu , Haiwen Li , Yanming Wang

Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…

Quantitative Methods · Quantitative Biology 2018-01-04 Sam Sinai , Eric Kelsic , George M. Church , Martin A. Nowak

The growing significance of RNA engineering in diverse biological applications has spurred interest in developing AI methods for structure-based RNA design. While diffusion models have excelled in protein design, adapting them for RNA…

Biomolecules · Quantitative Biology 2024-06-11 Divya Nori , Wengong Jin

The past two years have witnessed the evolution of large language model (LLM)-based multi-agent systems from labor-intensive manual design to partial automation (\textit{e.g.}, prompt engineering, communication topology) and eventually to…

Machine Learning · Computer Science 2025-02-12 Guibin Zhang , Kaijie Chen , Guancheng Wan , Heng Chang , Hong Cheng , Kun Wang , Shuyue Hu , Lei Bai

Protein sequence data from nature exhibits survivorship bias: we only observe data from those organisms that survive and reproduce, while non-functional protein mutations are eliminated by natural selection. Thus, predicting whether a…

Machine Learning · Computer Science 2026-05-11 Zhongmou Chao , Poompol Buathong , Ekaterina Selivanovitch , Susan Daniel , Peter I. Frazier

Flow matching models have emerged as a strong alternative to diffusion models, but existing inversion and editing methods designed for diffusion are often ineffective or inapplicable to them. The straight-line, non-crossing trajectories of…

Computer Vision and Pattern Recognition · Computer Science 2026-05-21 Guanlong Jiao , Biqing Huang , Kuan-Chieh Wang , Renjie Liao

Proteins are essential for almost all biological processes and derive their diverse functions from complex 3D structures, which are in turn determined by their amino acid sequences. In this paper, we exploit the rich biological inductive…

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