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We derive a novel generative model from iterative Gaussian posterior inference. By treating the generated sample as an unknown variable, we can formulate the sampling process in the language of Bayesian probability. Our model uses a…

Machine Learning · Computer Science 2026-01-28 Marten Lienen , Marcel Kollovieh , Stephan Günnemann

Combining discrete and continuous data is an important capability for generative models. We present Discrete Flow Models (DFMs), a new flow-based model of discrete data that provides the missing link in enabling flow-based generative models…

Machine Learning · Statistics 2024-06-07 Andrew Campbell , Jason Yim , Regina Barzilay , Tom Rainforth , Tommi Jaakkola

Computational protein design facilitates discovery of novel proteins with prescribed structure and functionality. Exciting designs were recently reported using novel data-driven methodologies that can be roughly divided into two categories:…

Biological Physics · Physics 2023-03-28 Cyril Malbranke , David Bikard , Simona Cocco , Rémi Monasson , Jérôme Tubiana

Composed of amino acid chains that influence how they fold and thus dictating their function and features, proteins are a class of macromolecules that play a central role in major biological processes and are required for the structure,…

Quantitative Methods · Quantitative Biology 2022-07-15 Aaron Wang

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

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

Protein design is the inverse approach of the three-dimensional (3D) structure prediction for elucidating the relationship between the 3D structures and amino acid sequences. In general, the computation of the protein design involves a…

Biological Physics · Physics 2021-07-14 Tomoei Takahashi , George Chikenji , Kei Tokita

Here we introduce a new design framework for synthetic biology that exploits the advantages of Bayesian model selection. We will argue that the difference between inference and design is that in the former we try to reconstruct the system…

Molecular Networks · Quantitative Biology 2015-05-27 Chris Barnes , Daniel Silk , Xia Sheng , Michael P. H. Stumpf

Directed evolution is a versatile technique in protein engineering that mimics the process of natural selection by iteratively alternating between mutagenesis and screening in order to search for sequences that optimize a given property of…

Biomolecules · Quantitative Biology 2024-05-02 Lixue Cheng , Ziyi Yang , Changyu Hsieh , Benben Liao , Shengyu Zhang

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

Advanced generative model (e.g., diffusion model) derived from simplified continuity assumptions of data distribution, though showing promising progress, has been difficult to apply directly to geometry generation applications due to the…

Chemical Physics · Physics 2024-03-26 Yuxuan Song , Jingjing Gong , Yanru Qu , Hao Zhou , Mingyue Zheng , Jingjing Liu , Wei-Ying Ma

Protein backbone generation plays a central role in de novo protein design and is significant for many biological and medical applications. Although diffusion and flow-based generative models provide potential solutions to this challenging…

Machine Learning · Computer Science 2025-05-29 Angxiao Yue , Zichong Wang , Hongteng Xu

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

Biomolecules · Quantitative Biology 2024-10-03 Chentong Wang , Sarah Alamdari , Carles Domingo-Enrich , Ava Amini , Kevin K. Yang

Proteins are the basic building blocks of life. They usually perform functions by folding to a particular structure. Understanding the folding process could help the researchers to understand the functions of proteins and could also help to…

Computational Engineering, Finance, and Science · Computer Science 2015-10-21 Jianzhu Ma

Protein fitness optimization involves finding a protein sequence that maximizes desired quantitative properties in a combinatorially large design space of possible sequences. Recent advances in steering protein generative models (e.g.,…

Biomolecules · Quantitative Biology 2025-10-22 Jason Yang , Wenda Chu , Daniel Khalil , Raul Astudillo , Bruce J. Wittmann , Frances H. Arnold , Yisong Yue

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

Accurate localization of proteins from fluorescence microscopy images is challenging due to the inter-class similarities and intra-class disparities introducing grave concerns in addressing multi-class classification problems. Conventional…

Computer Vision and Pattern Recognition · Computer Science 2021-10-11 Muhammad Tahir , Saeed Anwar , Ajmal Mian , Abdul Wahab Muzaffar

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

We review the recent progress in computational approaches to protein design which builds on advances in statistical-mechanical protein folding theory. In particular, we evaluate the degeneracy of the protein code (i.e. how many sequences…

Condensed Matter · Physics 2007-05-23 E. I. Shakhnovich

We introduce a generative model for protein backbone design utilizing geometric products and higher order message passing. In particular, we propose Clifford Frame Attention (CFA), an extension of the invariant point attention (IPA)…

Machine Learning · Computer Science 2024-11-11 Simon Wagner , Leif Seute , Vsevolod Viliuga , Nicolas Wolf , Frauke Gräter , Jan Stühmer