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Bayesian posterior inference is prevalent in various machine learning problems. Variational inference provides one way to approximate the posterior distribution, however its expressive power is limited and so is the accuracy of resulting…

Machine Learning · Computer Science 2018-07-11 Guoqing Zheng , Yiming Yang , Jaime Carbonell

Directed evolution is an iterative laboratory process of designing proteins with improved function by iteratively synthesizing new protein variants and evaluating their desired property with expensive and time-consuming biochemical…

Machine Learning · Computer Science 2025-09-08 Matouš Soldát , Jiří Kléma

We study how to generate molecule conformations (i.e., 3D structures) from a molecular graph. Traditional methods, such as molecular dynamics, sample conformations via computationally expensive simulations. Recently, machine learning…

Machine Learning · Computer Science 2021-04-01 Minkai Xu , Shitong Luo , Yoshua Bengio , Jian Peng , Jian Tang

Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure,…

Biomolecules · Quantitative Biology 2025-03-04 Petr Kouba , Joan Planas-Iglesias , Jiri Damborsky , Jiri Sedlar , Stanislav Mazurenko , Josef Sivic

Learning energy-based model (EBM) requires MCMC sampling of the learned model as an inner loop of the learning algorithm. However, MCMC sampling of EBMs in high-dimensional data space is generally not mixing, because the energy function,…

Machine Learning · Statistics 2022-03-17 Erik Nijkamp , Ruiqi Gao , Pavel Sountsov , Srinivas Vasudevan , Bo Pang , Song-Chun Zhu , Ying Nian Wu

Molecular dynamics (MD) is a crucial technique for simulating biological systems, enabling the exploration of their dynamic nature and fostering an understanding of their functions and properties. To address exploration inefficiency,…

Quantitative Methods · Quantitative Biology 2024-05-03 Shaoning Li , Yusong Wang , Mingyu Li , Jian Zhang , Bin Shao , Nanning Zheng , Jian Tang

The structure of a protein is crucial in determining its functionality, and is much more conserved than sequence during evolution. A key task in structural biology is to compare protein structures in order to determine evolutionary…

Methodology · Statistics 2019-11-06 Christopher Fallaize , Peter Green , Kanti Mardia , Stuart Barber

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.…

Modeling stochastic dynamics from discrete observations is a key interdisciplinary challenge. Existing methods often fail to estimate the continuous evolution of probability densities from trajectories or face the curse of dimensionality.…

Computational Engineering, Finance, and Science · Computer Science 2025-12-02 Ruikun Li , Jiazhen Liu , Huandong Wang , Qingmin Liao , Yong Li

Diffusion generative models have emerged as a powerful framework for addressing problems in structural biology and structure-based drug design. These models operate directly on 3D molecular structures. Due to the unfavorable scaling of…

Biomolecules · Quantitative Biology 2024-05-10 Ian Dunn , David Ryan Koes

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

Finding semantic correspondences is a challenging problem. With the breakthrough of CNNs stronger features are available for tasks like classification but not specifically for the requirements of semantic matching. In the following we…

Computer Vision and Pattern Recognition · Computer Science 2019-06-18 Nikolai Ufer , Kam To Lui , Katja Schwarz , Paul Warkentin , Björn Ommer

Current discriminative depth estimation methods often produce blurry artifacts, while generative approaches suffer from slow sampling due to curvatures in the noise-to-depth transport. Our method addresses these challenges by framing depth…

Computer Vision and Pattern Recognition · Computer Science 2024-12-20 Ming Gui , Johannes Schusterbauer , Ulrich Prestel , Pingchuan Ma , Dmytro Kotovenko , Olga Grebenkova , Stefan Andreas Baumann , Vincent Tao Hu , Björn Ommer

We present Preference Flow Matching (PFM), a new framework for preference-based reinforcement learning (PbRL) that streamlines the integration of preferences into an arbitrary class of pre-trained models. Existing PbRL methods require…

Machine Learning · Computer Science 2024-10-29 Minu Kim , Yongsik Lee , Sehyeok Kang , Jihwan Oh , Song Chong , Se-Young Yun

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…

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

Sequential probabilistic inference from streaming observations requires modeling distributions over future trajectories as new observations arrive. Although diffusion and flow-matching models are effective at capturing high-dimensional,…

Machine Learning · Computer Science 2026-05-15 Yinan Huang , Hans Hao-Hsun Hsu , Junran Wang , Bo Dai , Pan Li

This paper focuses on the alignment of flow matching models with human preferences. A promising way is fine-tuning by directly backpropagating reward gradients through the differentiable generation process of flow matching. However,…

Computer Vision and Pattern Recognition · Computer Science 2026-05-05 Zhanhao Liang , Tao Yang , Jie Wu , Chengjian Feng , Liang Zheng

We propose a generative multivariate posterior sampler via flow matching. It offers a simple training objective, and does not require access to likelihood evaluation. The method learns a dynamic, block-triangular velocity field in the joint…

Machine Learning · Statistics 2026-04-02 Percy S. Zhai , So Won Jeong , Veronika Ročková

Bayesian filtering and smoothing for high-dimensional nonlinear dynamical systems are fundamental yet challenging problems in many areas of science and engineering. In this work, we propose FLUID, a flow-based unified amortized inference…

Machine Learning · Statistics 2026-04-27 Tiangang Cui , Xiaodong Feng , Chenlong Pei , Xiaoliang Wan , Tao Zhou