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For many chemical processes the accurate description of solvent effects are vitally important. Here, we describe a hybrid ansatz for the explicit quantum mechanical description of solute-solvent and solvent-solvent interactions based on…

Normalizing flows can transform a simple prior probability distribution into a more complex target distribution. Here, we evaluate the ability and efficiency of generative machine learning methods to sample the Boltzmann distribution of an…

Soft Condensed Matter · Physics 2024-09-16 Gerhard Jung , Giulio Biroli , Ludovic Berthier

Sampling diverse, thermodynamically feasible molecular conformations plays a crucial role in predicting properties of a molecule. In this paper we propose to use GFlowNet for sampling conformations of small molecules from the Boltzmann…

The determination of the solvation free energy of ions and molecules holds profound importance across a spectrum of applications spanning chemistry, biology, energy storage, and the environment. Molecular dynamics simulations are a powerful…

Mesoscale and Nanoscale Physics · Physics 2023-11-28 Zhou Yu , Enrique R. Batista , Ping Yang , Danny Perez

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

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

In this work, we consider the problem of training a generator from evaluations of energy functions or unnormalized densities. This is a fundamental problem in probabilistic inference, which is crucial for scientific applications such as…

Machine Learning · Computer Science 2024-08-30 Dongyeop Woo , Sungsoo Ahn

The double distribution function approach is an efficient route towards extension of kinetic solvers to compressible flows. With a number of realizations available, an overview and comparative study in the context of high speed compressible…

Fluid Dynamics · Physics 2024-05-21 S. A. Hosseini , A. Bhadauria , I. V. Karlin

One reason that free energy difference calculations are notoriously difficult in molecular systems is due to insufficient conformational overlap, or similarity, between the two states or systems of interest. The degree of overlap is…

Biological Physics · Physics 2009-11-11 F. Marty Ytreberg , Daniel M. Zuckerman

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

The pseudopotential and free energy models are two popular extensions of the lattice Boltzmann method for multiphase flows. Until now, they have been developed apart from each other in the literature. However, important questions about…

Normalizing flows are a promising tool for modeling probability distributions in physical systems. While state-of-the-art flows accurately approximate distributions and energies, applications in physics additionally require smooth energies…

Machine Learning · Statistics 2021-12-01 Jonas Köhler , Andreas Krämer , Frank Noé

Exploring the free-energy landscape along reaction coordinates or system parameters $\lambda$ is central to many studies of high-dimensional model systems in physics, e.g. large molecules or spin glasses. In simulations this usually…

Statistical Mechanics · Physics 2018-09-05 Viveca Lindahl , Jack Lidmar , Berk Hess

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

We propose a predictive Density Functional Theory (DFT) for the calculation of solvation free energies. Our approach is based on a Helmholtz free-energy functional that is consistent with the perturbed-chain SAFT (PC-SAFT) equation of…

Chemical Physics · Physics 2021-07-07 Johannes Eller , Tanja Matzerath , Thijs van Westen , Joachim Gross

Determining the solvation free energies of single ions in water is one of the most fundamental problems in physical chemistry and yet many unresolved questions remain. In particular, the ability to decompose the solvation free energy into…

Chemical Physics · Physics 2017-11-21 Timothy T. Duignan , Marcel D. Baer , Gregory K. Schenter , Christopher J. Mundy

Free energies govern the behavior of soft and liquid matter, and improving their predictions could have a large impact on the development of drugs, electrolytes or homogeneous catalysts. Unfortunately, it is challenging to devise an…

Chemical Physics · Physics 2021-04-14 Jan Weinreich , Nicholas J. Browning , O. Anatole von Lilienfeld

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

In transitions between different environmental settings, a molecular system inevitably undergoes a range of detectable changes, and the ability to accurately simulate such responses, e.g., in the form of shifts to molecular energies,…

Chemical Physics · Physics 2026-01-14 Kasper F. Schaltz , Jonas Greiner , Filippo Lipparini , Janus J. Eriksen

Employing a classical density-functional description of liquid environments, we introduce a rigorous method for the diffusion quantum Monte Carlo calculation of free energies and thermodynamic averages of solvated systems that requires…