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High-quality training datasets are crucial for the development of effective protein design models, but existing synthetic datasets often include unfavorable sequence-structure pairs, impairing generative model performance. We leverage…

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…

Proteins typically exist in complexes, interacting with other proteins or biomolecules to perform their specific biological roles. Research on single-chain protein modeling has been extensively and deeply explored, with advancements seen in…

Machine Learning · Computer Science 2025-09-09 Ruizhe Chen , Dongyu Xue , Xiangxin Zhou , Zaixiang Zheng , Xiangxiang Zeng , Quanquan Gu

We present A-CODE, a fully atomic unified one-stage protein co-design model that simultaneously refines discrete atom types and continuous atom coordinates. Unlike predominant two-stage methods that cascade structure design with amino…

Quantitative Methods · Quantitative Biology 2026-05-06 Chaoran Cheng , Jiaqi Guan , Milong Ren , Chengyue Gong , Cong Liu , Xinshi Chen , Ge Liu , Wenzhi Xiao

Proteins are complex biomolecules that perform a variety of crucial functions within living organisms. Designing and generating novel proteins can pave the way for many future synthetic biology applications, including drug discovery.…

Designing novel proteins that bind to small molecules is a long-standing challenge in computational biology, with applications in developing catalysts, biosensors, and more. Current computational methods rely on the assumption that the…

Biomolecules · Quantitative Biology 2024-09-19 Junqi Liu , Shaoning Li , Chence Shi , Zhi Yang , Jian Tang

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

The protein design problem involves finding polypeptide sequences folding into a given threedimensional structure. Its rigorous algorithmic solution is computationally demanding, involving a nested search in sequence and structure spaces.…

Quantum Physics · Physics 2024-07-11 Veronica Panizza , Philipp Hauke , Cristian Micheletti , Pietro Faccioli

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

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

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

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

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction,…

Biomolecules · Quantitative Biology 2022-11-28 Kevin E. Wu , Kevin K. Yang , Rianne van den Berg , James Y. Zou , Alex X. Lu , Ava P. Amini

We introduce RNA-FrameFlow, the first generative model for 3D RNA backbone design. We build upon SE(3) flow matching for protein backbone generation and establish protocols for data preparation and evaluation to address unique challenges…

Investigating conformational landscapes of proteins is a crucial way to understand their biological functions and properties. AlphaFlow stands out as a sequence-conditioned generative model that introduces flexibility into structure…

Machine Learning · Computer Science 2024-07-18 Shaoning Li , Mingyu Li , Yusong Wang , Xinheng He , Nanning Zheng , Jian Zhang , Pheng-Ann Heng

Protein folding and design are major biophysical problems, the solution of which would lead to important applications especially in medicine. Here a novel protein model capable of simultaneously provide quantitative protein design and…

Biological Physics · Physics 2015-06-22 Ivan Coluzza

Generating diverse, all-atom conformational ensembles of dynamic proteins such as G-protein-coupled receptors (GPCRs) is critical for understanding their function, yet most generative models simplify atomic detail or ignore conformational…

Biomolecules · Quantitative Biology 2025-08-19 Aditya Sengar , Ali Hariri , Daniel Probst , Patrick Barth , Pierre Vandergheynst

In recent years, there has been a surge in the development of 3D structure-based pre-trained protein models, representing a significant advancement over pre-trained protein language models in various downstream tasks. However, most existing…

Machine Learning · Computer Science 2024-06-04 Jiale Zhao , Wanru Zhuang , Jia Song , Yaqi Li , Shuqi Lu

Peptides, short chains of amino acid residues, play a vital role in numerous biological processes by interacting with other target molecules, offering substantial potential in drug discovery. In this work, we present PepFlow, the first…

Biomolecules · Quantitative Biology 2024-06-04 Jiahan Li , Chaoran Cheng , Zuofan Wu , Ruihan Guo , Shitong Luo , Zhizhou Ren , Jian Peng , Jianzhu Ma

Excitement at the prospect of using data-driven generative models to sample configurational ensembles of biomolecular systems stems from the extraordinary success of these models on a diverse set of high-dimensional sampling tasks. Unlike…

Statistical Mechanics · Physics 2024-02-06 Shriram Chennakesavalu , Grant M. Rotskoff
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