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Flow-based Generative Models (FGMs) effectively transform noise into complex data distributions. Incorporating Optimal Transport (OT) to couple noise and data during FGM training has been shown to improve the straightness of flow…

Machine Learning · Computer Science 2025-10-20 Lingkai Kong , Molei Tao , Yang Liu , Bryan Wang , Jinmiao Fu , Chien-Chih Wang , Huidong Liu

Generative models for de novo protein backbone design have achieved remarkable success in creating novel protein structures. However, these diffusion-based approaches remain computationally intensive and slower than desired for large-scale…

Machine Learning · Computer Science 2026-02-09 Shentong Mo , Lanqing Li

This paper proposes a novel method, Explicit Flow Matching (ExFM), for training and analyzing flow-based generative models. ExFM leverages a theoretically grounded loss function, ExFM loss (a tractable form of Flow Matching (FM) loss), to…

Machine Learning · Computer Science 2024-07-03 Gleb Ryzhakov , Svetlana Pavlova , Egor Sevriugov , Ivan Oseledets

Generative models emerge as promising candidates for novel sequence-data driven approaches to protein design, and for the extraction of structural and functional information about proteins deeply hidden in rapidly growing sequence…

Biomolecules · Quantitative Biology 2021-11-10 Jeanne Trinquier , Guido Uguzzoni , Andrea Pagnani , Francesco Zamponi , Martin Weigt

Coarse-grained (CG) molecular models of proteins can substantially increase the time and length scales accessible to molecular dynamics simulations of proteins, but recovery of accurate all-atom (AA) ensembles from CG simulation…

Chemical Physics · Physics 2025-08-06 Alex Berlaga , Michael S. Jones , Andrew L. Ferguson

Structure-based drug design (SBDD) leverages the 3D structure of biomolecular targets to guide the creation of new therapeutic agents. Recent advances in generative models, including diffusion models and geometric deep learning, have…

Biomolecules · Quantitative Biology 2025-01-28 Ali Khodabandeh Yalabadi , Mehdi Yazdani-Jahromi , Ozlem Ozmen Garibay

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

Generative models of macromolecules carry abundant and impactful implications for industrial and biomedical efforts in protein engineering. However, existing methods are currently limited to modeling protein structures or sequences,…

Biomolecules · Quantitative Biology 2024-01-15 Alex Morehead , Jeffrey Ruffolo , Aadyot Bhatnagar , Ali Madani

Generating novel active molecules for a given protein is an extremely challenging task for generative models that requires an understanding of the complex physical interactions between the molecule and its environment. In this paper, we…

Functional data, i.e., smooth random functions observed over a continuous domain, are increasingly available in areas such as biomedical research, health informatics, and epidemiology. However, effective statistical analysis for functional…

Machine Learning · Statistics 2026-04-07 Jianbin Tan , Anru R. Zhang

Sampling from unnormalized target distributions, e.g.\ Boltzmann distributions $\mu_{\text{target}}(x) \propto \exp(-E(x)/T)$, is fundamental to many scientific applications yet computationally challenging due to complex, high-dimensional…

Machine Learning · Statistics 2026-04-22 Niclas Dern , Lennart Redl , Sebastian Pfister , Marcel Kollovieh , David Lüdke , Stephan Günnemann

Flow-matching models have recently emerged as a powerful framework for continuous generative modeling, including 3D point cloud synthesis. However, their deployment is limited by the need for multiple sequential sampling steps at inference…

Machine Learning · Computer Science 2026-03-20 Elaheh Akbari , Shansita Sharma , Ping He , Ahmadreza Moradipari , Kyungtae Han , Hamed Pirsiavash , Yikun Bai , Soheil Kolouri

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

Equivariant diffusion models have achieved impressive performance in 3D molecule generation. These models incorporate Euclidean symmetries of 3D molecules by utilizing an SE(3)-equivariant denoising network. However, specialized equivariant…

Machine Learning · Computer Science 2025-07-01 Yuhui Ding , Thomas Hofmann

We present Riemannian Gaussian Variational Flow Matching (RG-VFM), a geometric extension of Variational Flow Matching (VFM) for generative modeling on manifolds. Motivated by the benefits of VFM, we derive a variational flow matching…

Machine Learning · Computer Science 2026-03-13 Olga Zaghen , Floor Eijkelboom , Alison Pouplin , Cong Liu , Max Welling , Jan-Willem van de Meent , Erik J. Bekkers

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

The advent of highly accurate protein structure prediction methods has fueled an exponential expansion of the protein structure database. Consequently, there is a rising demand for rapid and precise structural homolog search. Traditional…

Biomolecules · Quantitative Biology 2023-12-01 Yuan Liu , Hong-Bin Shen

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

Designing protein sequences that fold into a target 3-D structure, termed as the inverse folding problem, is central to protein engineering. However, it remains challenging due to the vast sequence space and the importance of local…

Quantitative Methods · Quantitative Biology 2026-03-17 Sazan Mahbub , Souvik Kundu , Eric P. Xing

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