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We present a new method to compute free energies at a quantum mechanical (QM) level of theory from molecular simulations using cheap reference potential energy functions, such as force fields. To overcome the poor overlap between the…

Computational Physics · Physics 2023-11-13 Andrea Rizzi , Paolo Carloni , Michele Parrinello

Existing adaptive bias techniques, which seek to estimate free energies and physical properties from molecular simulations, are limited by their reliance on fixed kernels or basis sets which hinder their ability to efficiently conform to…

Statistical Mechanics · Physics 2018-04-04 Hythem Sidky , Jonathan K. Whitmer

This report presents the application of polynomial regression for estimating free energy differences using thermodynamic integration. We employ linear regression to construct a polynomial that optimally fits the thermodynamic integration…

Computational Physics · Physics 2008-10-02 Conrad Shyu , F. Marty Ytreberg

We present a detailed comparison of computational efficiency and precision for several free energy difference ($\Delta F$) methods. The analysis includes both equilibrium and non-equilibrium approaches, and distinguishes between…

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

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

Free energies play a central role in characterising the behaviour of chemical systems and are among the most important quantities that can be calculated by molecular dynamics simulations. Solvation free energies in various organic solvents,…

Chemical Physics · Physics 2026-02-11 J. Harry Moore , Daniel J. Cole , Gabor Csanyi

We apply reinforcement learning (RL) to robotics tasks. One of the drawbacks of traditional RL algorithms has been their poor sample efficiency. One approach to improve the sample efficiency is model-based RL. In our model-based RL…

Machine Learning · Computer Science 2023-05-16 Adithya Ramesh , Balaraman Ravindran

Accurate free energy representations are crucial for understanding phase dynamics in materials. We employ a scale-bridging approach to incorporate atomistic information into our free energy model by training a neural network on DFT-informed…

Computational Physics · Physics 2025-03-12 Jamie Holber , Krishna Garikipati

This work presents a robust, energy-based deep learning framework for solving transmission problems in heterogeneous media, including cases with discontinuous material scenarios. We introduce a weighted First-Order System Least-Squares…

Numerical Analysis · Mathematics 2026-04-21 Alejandro Duque , Paulina Sepúlveda , Carlos Uriarte , Jamie M. Taylor , David Pardo

Deep learning has shown strong potential in modeling complex spatiotemporal dynamics. However, most existing methods depend on densely and uniformly sampled data, which is often unavailable in practice due to sensor and cost limitations. In…

Machine Learning · Computer Science 2025-12-16 Han Wan , Qi Wang , Yuan Mi , Rui Zhang , Hao Sun

Metadynamics is a powerful computational tool to obtain the free energy landscape of complex systems. The Monte Carlo algorithm has proven useful to calculate thermodynamic quantities associated with simplified models of proteins, and thus…

Statistical Mechanics · Physics 2007-10-04 F. Marini , C. Camilloni , D. Provasi , R. A. Broglia , G. Tiana

In recent years, diffusion models trained on equilibrium molecular distributions have proven effective for sampling biomolecules. Beyond direct sampling, the score of such a model can also be used to derive the forces that act on molecular…

Machine Learning · Computer Science 2026-01-15 Michael Plainer , Hao Wu , Leon Klein , Stephan Günnemann , Frank Noé

In this paper we first analyzed the inductive bias underlying the data scattered across complex free energy landscapes (FEL), and exploited it to train deep neural networks which yield reduced and clustered representation for the FEL. Our…

Statistical Mechanics · Physics 2021-03-19 Jun Zhang , Yao-Kun Lei , Xing Che , Zhen Zhang , Yi Isaac Yang , Yi Qin Gao

Exploratory Landscape Analysis is a powerful technique for numerically characterizing landscapes of single-objective continuous optimization problems. Landscape insights are crucial both for problem understanding as well as for assessing…

Machine Learning · Computer Science 2022-04-15 Moritz Vinzent Seiler , Raphael Patrick Prager , Pascal Kerschke , Heike Trautmann

The free energy plays a fundamental role in descriptions of many systems in continuum physics. Notably, in multiphysics applications, it encodes thermodynamic coupling between different fields. It thereby gives rise to driving forces on the…

Machine Learning · Computer Science 2023-07-19 Gregory Teichert , Anirudh Natarajan , Anton Van der Ven , Krishna Garikipati

Enhanced sampling methods such as metadynamics and umbrella sampling have become essential tools for exploring the configuration space of molecules and materials. At the same time, they have long faced a number of issues such as the…

Chemical Physics · Physics 2021-12-28 Dongdong Wang , Yanze Wang , Junhan Chang , Linfeng Zhang , Han Wang , Weinan E

Molecular dynamics is a powerful tool for studying the thermodynamics and kinetics of complex molecular events. However, these simulations can rarely sample the required time scales in practice. Transition path sampling overcomes this…

Chemical Physics · Physics 2023-07-31 Gianmarco Lazzeri , Hendrik Jung , Peter G. Bolhuis , Roberto Covino

Recent model-free reinforcement learning algorithms have proposed incorporating learned dynamics models as a source of additional data with the intention of reducing sample complexity. Such methods hold the promise of incorporating imagined…

Machine Learning · Computer Science 2018-03-02 Vladimir Feinberg , Alvin Wan , Ion Stoica , Michael I. Jordan , Joseph E. Gonzalez , Sergey Levine

The Fokker-Plank-Kolmogorov (FPK) equation is an idealized model representing many stochastic systems commonly encountered in the analysis of stochastic structures as well as many other applications. Its solution thus provides an invaluable…

Machine Learning · Computer Science 2023-11-09 Amir H. Khodabakhsh , Seid H. Pourtakdoust

Free-energy landscape theory is often used to describe complex molecular systems. Here, a microscopic description of water structure and dynamics based on configuration-space-networks and molecular dynamics simulations of the TIP4P/2005…

Statistical Mechanics · Physics 2015-06-05 Diego Prada-Gracia , Roman Shevchuk , Peter Hamm , Francesco Rao