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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

Diffusion- and flow-based generative models have recently demonstrated strong performance in protein backbone generation tasks, offering unprecedented capabilities for de novo protein design. However, while achieving notable performance in…

Machine Learning · Computer Science 2025-10-29 Liyang Xie , Haoran Zhang , Zhendong Wang , Wesley Tansey , Mingyuan Zhou

Generating novel and functional protein sequences is critical to a wide range of applications in biology. Recent advancements in conditional diffusion models have shown impressive empirical performance in protein generation tasks. However,…

Machine Learning · Computer Science 2025-12-04 Zinan Ling , Yi Shi , Brett McKinney , Da Yan , Yang Zhou , Bo Hui

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

Recently, many generative models for de novo protein structure design have emerged. Yet, only few tackle the difficult task of directly generating fully atomistic structures jointly with the underlying amino acid sequence. This is…

The computational design of novel protein structures has the potential to impact numerous scientific disciplines greatly. Toward this goal, we introduce FoldFlow, a series of novel generative models of increasing modeling power based on the…

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…

Through evolution, nature has presented a set of remarkable protein materials, including elastins, silks, keratins and collagens with superior mechanical performances that play crucial roles in mechanobiology. However, going beyond natural…

Materials Science · Physics 2023-12-19 Bo Ni , David L. Kaplan , Markus J. Buehler

Recent advances in geometric deep learning and generative modeling have enabled the design of novel proteins with a wide range of desired properties. However, current state-of-the-art approaches are typically restricted to generating…

Biomolecules · Quantitative Biology 2025-08-26 Vsevolod Viliuga , Leif Seute , Nicolas Wolf , Simon Wagner , Arne Elofsson , Jan Stühmer , Frauke Gräter

MOTIVATION: Proteins fold into complex structures that are crucial for their biological functions. Experimental determination of protein structures is costly and therefore limited to a small fraction of all known proteins. Hence, different…

Biomolecules · Quantitative Biology 2018-04-18 David Menéndez Hurtado , Karolis Uziela , Arne Elofsson

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…

Protein folding models have achieved groundbreaking results typically via a combination of integrating domain knowledge into the architectural blocks and training pipelines. Nonetheless, given the success of generative models across…

Machine Learning · Computer Science 2025-12-11 Yuyang Wang , Jiarui Lu , Navdeep Jaitly , Josh Susskind , Miguel Angel Bautista

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

We present FrameFlow, a method for fast protein backbone generation using SE(3) flow matching. Specifically, we adapt FrameDiff, a state-of-the-art diffusion model, to the flow-matching generative modeling paradigm. We show how flow…

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

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…

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

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

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

We propose a hierarchical protein backbone generative model that separates coarse and fine-grained details. Our approach called LSD consists of two stages: sampling latents which are decoded into a contact map then sampling atomic…

Quantitative Methods · Quantitative Biology 2025-04-15 Jason Yim , Marouane Jaakik , Ge Liu , Jacob Gershon , Karsten Kreis , David Baker , Regina Barzilay , Tommi Jaakkola
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