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Scalable sampling of molecular states in thermodynamic equilibrium is a long-standing challenge in statistical physics. Boltzmann generators tackle this problem by pairing normalizing flows with importance sampling to obtain uncorrelated…

Machine Learning · Computer Science 2026-01-21 Charlie B. Tan , Avishek Joey Bose , Chen Lin , Leon Klein , Michael M. Bronstein , Alexander Tong

The use of generative models to sample equilibrium distributions of many-body systems, as first demonstrated by Boltzmann Generators, has attracted substantial interest due to their ability to produce unbiased and uncorrelated samples in…

Statistical Mechanics · Physics 2025-10-23 Maximilian Schebek , Frank Noé , Jutta Rogal

Computing equilibrium states in condensed-matter many-body systems, such as solvated proteins, is a long-standing challenge. Lacking methods for generating statistically independent equilibrium samples in "one shot", vast computational…

Machine Learning · Statistics 2019-07-15 Frank Noé , Simon Olsson , Jonas Köhler , Hao Wu

Efficient sampling from the Boltzmann distribution given its energy function is a key challenge for modeling complex physical systems such as molecules. Boltzmann Generators address this problem by leveraging continuous normalizing flows to…

Machine Learning · Computer Science 2025-10-17 Rishal Aggarwal , Jacky Chen , Nicholas M. Boffi , David Ryan Koes

Sampling equilibrium molecular configurations from the Boltzmann distribution is a longstanding challenge. Boltzmann Generators (BGs) address this by combining exact-likelihood generative models with importance sampling, but practical…

Machine Learning · Computer Science 2026-05-29 Weilong Chen , Bojun Zhao , Jan Eckwert , Julija Zavadlav

Sampling equilibrium distributions is fundamental to statistical mechanics. While flow matching has emerged as scalable state-of-the-art paradigm for generative modeling, its potential for equilibrium sampling in condensed-phase systems…

Computational Physics · Physics 2026-03-31 Emil Hoffmann , Maximilian Schebek , Leon Klein , Frank Noé , Jutta Rogal

The Boltzmann distribution of a protein provides a roadmap to all of its functional states. Normalizing flows are a promising tool for modeling this distribution, but current methods are intractable for typical pharmacological targets; they…

Machine Learning · Computer Science 2024-01-10 Joseph C. Kim , David Bloore , Karan Kapoor , Jun Feng , Ming-Hong Hao , Mengdi Wang

Generative models based on invertible transformations provide a physics-aware route to sample equilibrium configurations directly from the Boltzmann distribution, enabling efficient exploration of complex thermodynamic landscapes. Here, we…

Statistical Mechanics · Physics 2026-03-06 Luigi de Santis , John Russo , Andrea Ninarello

Molecular conformer generation is a fundamental task in computational chemistry. Several machine learning approaches have been developed, but none have outperformed state-of-the-art cheminformatics methods. We propose torsional diffusion, a…

Chemical Physics · Physics 2023-03-02 Bowen Jing , Gabriele Corso , Jeffrey Chang , Regina Barzilay , Tommi Jaakkola

Efficient sampling from high-dimensional and multimodal unnormalized probability distributions is a central challenge in many areas of science and machine learning. We focus on Boltzmann generators (BGs) that aim to sample the Boltzmann…

Machine Learning · Computer Science 2026-03-03 Christopher von Klitzing , Denis Blessing , Henrik Schopmans , Pascal Friederich , Gerhard Neumann

Boltzmann Generators have emerged as a promising machine learning tool for generating samples from equilibrium distributions of molecular systems using Normalizing Flows and importance weighting. Recently, Flow Matching has helped speed up…

Machine Learning · Statistics 2025-10-21 Lorenz Vaitl , Leon Klein

Boltzmann generators approach the sampling problem in many-body physics by combining a normalizing flow and a statistical reweighting method to generate samples in thermodynamic equilibrium. The equilibrium distribution is usually defined…

Statistical Mechanics · Physics 2022-09-07 Manuel Dibak , Leon Klein , Andreas Krämer , Frank Noé

The paper by No\'e et al. [F. No\'e, S. Olsson, J. K\"ohler and H. Wu, Science, 365:6457 (2019)] introduced the concept of Boltzmann Generators (BGs), a deep generative model that can produce unbiased independent samples of many-body…

We review Boltzmann machines and energy-based models. A Boltzmann machine defines a probability distribution over binary-valued patterns. One can learn parameters of a Boltzmann machine via gradient based approaches in a way that log…

Neural and Evolutionary Computing · Computer Science 2019-01-21 Takayuki Osogami

Sampling molecular conformations from the Boltzmann distribution is essential for computational chemistry, but iterative diffusion methods are prohibitively slow. Drifting Models offer one-step generation, yet their equilibrium matches the…

Chemical Physics · Physics 2026-03-09 Pipi Hu

Efficient sampling of unnormalized probability densities such as the Boltzmann distribution of molecular systems is a longstanding challenge. Next to conventional approaches like molecular dynamics or Markov chain Monte Carlo, variational…

Machine Learning · Computer Science 2025-06-18 Henrik Schopmans , Pascal Friederich

Generating stable molecular conformations is crucial in several drug discovery applications, such as estimating the binding affinity of a molecule to a target. Recently, generative machine learning methods have emerged as a promising, more…

Flows are exact-likelihood generative neural networks that transform samples from a simple prior distribution to the samples of the probability distribution of interest. Boltzmann Generators (BG) combine flows and statistical mechanics to…

Machine Learning · Statistics 2019-10-03 Jonas Köhler , Leon Klein , Frank Noé

The Boltzmann model for the random generation of "decomposable" combinatorial structures is a set of techniques that allows for efficient random sampling algorithms for a large class of families of discrete objects. The usual requirement of…

Data Structures and Algorithms · Computer Science 2011-12-23 Philippe Duchon

The accurate prediction of phase diagrams is of central importance for both the fundamental understanding of materials as well as for technological applications in material sciences. However, the computational prediction of the relative…

Statistical Mechanics · Physics 2024-11-26 Maximilian Schebek , Michele Invernizzi , Frank Noé , Jutta Rogal
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