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A generative model capable of sampling realistic molecules with desired properties could accelerate chemical discovery across a wide range of applications. Toward this goal, significant effort has focused on developing models that jointly…

Machine Learning · Computer Science 2025-08-19 Ian Dunn , David R. Koes

Deep generative models that produce novel molecular structures have the potential to facilitate chemical discovery. Diffusion models currently achieve state of the art performance for 3D molecule generation. In this work, we explore the use…

Biomolecules · Quantitative Biology 2024-05-01 Ian Dunn , David Ryan Koes

Amorphous molecular solids offer a promising alternative to inorganic semiconductors, owing to their mechanical flexibility and solution processability. The packing structure of these materials plays a crucial role in determining their…

Finding a suitable layout represents a crucial task for diverse applications in graphic design. Motivated by simpler and smoother sampling trajectories, we explore the use of Flow Matching as an alternative to current diffusion-based layout…

Computer Vision and Pattern Recognition · Computer Science 2024-07-16 Julian Jorge Andrade Guerreiro , Naoto Inoue , Kento Masui , Mayu Otani , Hideki Nakayama

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

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…

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

Development of scoring functions (SFs) used to predict protein-ligand binding energies requires high-quality 3D structures and binding assay data for training and testing their parameters. In this work, we show that one of the widely-used…

Biological Physics · Physics 2025-03-10 Yingze Wang , Kunyang Sun , Jie Li , Xingyi Guan , Oufan Zhang , Dorian Bagni , Teresa Head-Gordon

Flow matching models have emerged as a powerful framework for realistic image generation by learning to reverse a corruption process that progressively adds Gaussian noise. However, because noise is injected in the latent domain, its impact…

Computer Vision and Pattern Recognition · Computer Science 2026-04-20 Sucheng Ren , Qihang Yu , Ju He , Xiaohui Shen , Alan Yuille , Liang-Chieh Chen

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

In recent years machine learning (ML) took bio- and cheminformatics fields by storm, providing new solutions for a vast repertoire of problems related to protein sequence, structure, and interactions analysis. ML techniques, deep neural…

Biomolecules · Quantitative Biology 2020-03-31 Marta M. Stepniewska-Dziubinska , Piotr Zielenkiewicz , Pawel Siedlecki

We propose Pullback Flow Matching (PFM), a novel framework for generative modeling on data manifolds. Unlike existing methods that assume or learn restrictive closed-form manifold mappings for training Riemannian Flow Matching (RFM) models,…

Machine Learning · Computer Science 2025-07-10 Friso de Kruiff , Erik Bekkers , Ozan Öktem , Carola-Bibiane Schönlieb , Willem Diepeveen

Therapeutic peptides have proven to have great pharmaceutical value and potential in recent decades. However, methods of AI-assisted peptide drug discovery are not fully explored. To fill the gap, we propose a target-aware peptide design…

Biomolecules · Quantitative Biology 2024-12-10 Haitao Lin , Odin Zhang , Huifeng Zhao , Dejun Jiang , Lirong Wu , Zicheng Liu , Yufei Huang , Stan Z. Li

Determining the binding pose of a ligand to a protein, known as molecular docking, is a fundamental task in drug discovery. Generative approaches promise faster, improved, and more diverse pose sampling than physics-based methods, but are…

Machine Learning · Computer Science 2026-03-26 Alvaro Prat , Leo Zhang , Charlotte M. Deane , Yee Whye Teh , Garrett M. Morris

Flow matching (FM) has shown promising results in data-driven planning. However, it inherently lacks formal guarantees for ensuring state and action constraints, whose satisfaction is a fundamental and crucial requirement for the safety and…

Machine Learning · Computer Science 2025-12-02 Tzu-Yuan Huang , Armin Lederer , Dai-Jie Wu , Xiaobing Dai , Sihua Zhang , Stefan Sosnowski , Shao-Hua Sun , Sandra Hirche

The regulation of various cellular processes heavily relies on the protein complexes within a living cell, necessitating a comprehensive understanding of their three-dimensional structures to elucidate the underlying mechanisms. While…

Biomolecules · Quantitative Biology 2023-05-26 Yuanfeng Ji , Yatao Bian , Guoji Fu , Peilin Zhao , Ping Luo

Recent advances in cross-modal few-shot adaptation treat visual-semantic alignment as a continuous feature transport problem via Flow Matching (FM). However, we argue that Euclidean-based FM overlooks fundamental limitations of flat…

Computer Vision and Pattern Recognition · Computer Science 2026-02-25 Lin Li , Ziqi Jiang , Gefan Ye , Zhenqi He , Jiahui Li , Jun Xiao , Kwang-Ting Cheng , Long Chen

Modeling the interaction between proteins and ligands and accurately predicting their binding structures is a critical yet challenging task in drug discovery. Recent advancements in deep learning have shown promise in addressing this…

Machine Learning · Computer Science 2024-01-10 Qizhi Pei , Kaiyuan Gao , Lijun Wu , Jinhua Zhu , Yingce Xia , Shufang Xie , Tao Qin , Kun He , Tie-Yan Liu , Rui Yan

Many processes of scientific importance are characterized by time scales that extend far beyond the reach of standard simulation techniques. To circumvent this impediment a plethora of enhanced sampling methods has been developed. One…

Computational Physics · Physics 2018-12-05 Dan Mendels , Giovannimaria Piccini , Z. Faidon Brotzakis , Yi I. Yang , Michele Parrinello

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