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Related papers: Multi-Layer Free Energy Perturbation

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The free energy principle (FEP), as an encompassing framework and a unified brain theory, has been widely applied to account for various problems in fields such as cognitive science, neuroscience, social interaction, and hermeneutics. As a…

Neural and Evolutionary Computing · Computer Science 2023-06-13 Jingwei Liu

The rare-event sampling problem has long been the central limiting factor in molecular dynamics (MD), especially in biomolecular simulation. Recently, diffusion models such as BioEmu have emerged as powerful equilibrium samplers that…

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

We review uses of the generalized-ensemble algorithms for free-energy calculations in protein folding. Two of the well-known methods are multicanonical algorithm and replica-exchange method; the latter is also referred to as parallel…

Statistical Mechanics · Physics 2007-05-23 Y. Sugita , Y. Okamoto

In this paper we show how The Free Energy Principle (FEP) can provide an explanation for why real-world networks deviate from scale-free behaviour, and how these characteristic deviations can emerge from constraints on information…

Social and Information Networks · Computer Science 2025-02-19 Peter R Williams , Zhan Chen

The Free-Energy Principle (FEP) [1-3] has been adopted in a variety of ambitious proposals that aim to characterize all adaptive, sentient, and cognitive systems within a unifying framework. Judging by the amount of attention it has…

Neurons and Cognition · Quantitative Biology 2024-01-18 Zahra Sheikhbahaee , Adam Safron , Casper Hesp , Guillaume Dumas

Calculating free energy differences is a topic of substantial interest and has many applications including molecular docking and hydration, solvation, and binding free energies which is used in computational drug discovery. However, in…

Chemical Physics · Physics 2013-10-16 Asaf Farhi

Inspired by the recent development on calculating the free energy change via a relaxation process [Nat. Phys. 14, 842 (2018)], we investigate the role of heat released in an irreversible relaxation following a large perturbation. Utilizing…

Free energy profiles serve as a fundamental bridge between microscopic atomic fluctuations and macroscopic thermodynamic observables. Estimating the free energy profile along a reaction coordinate, referred to as the potential of mean force…

We present a method to explore the free energy landscapes of chemical reactions with post-transition-state bifurcations using an enhanced sampling method based on well-tempered metadynamics. Obviating the need for computationally expensive…

Chemical Physics · Physics 2023-04-18 Juno Nam , YounJoon Jung

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

A family of fast sampling methods is introduced here for molecular simulations of systems having rugged free energy landscapes. The methods represent a generalization of a strategy consisting of adjusting a model for the free energy as a…

Computational Physics · Physics 2022-02-07 Pablo F. Zubieta Rico , Juan J. de Pablo

Accurately predicting protein-ligand binding free energies (BFEs) remains a central challenge in drug discovery, particularly because the most reliable methods, such as free energy perturbation (FEP), are computationally intensive and…

Chemical Physics · Physics 2025-12-09 Farzad Molani , Art E. Cho

Molecular relaxation, finding the equilibrium state of a non-equilibrium structure, is an essential component of computational chemistry to understand reactivity. Classical force field (FF) methods often rely on insufficient local energy…

This article describes nonequilibrium techniques for the calculation of free energies of solids using molecular dynamics (MD) simulations. These methods provide an alternative to standard equilibrium thermodynamic integration methods and…

Materials Science · Physics 2022-01-13 Rodrigo Freitas , Mark Asta , Maurice de Koning

We introduce the Free Energy Manifold (FEM), a score-trained conditional energy model specialized for inference in hybrid Bayesian networks with discrete and continuous variables. FEM represents each conditional factor as an energy…

Machine Learning · Computer Science 2026-05-12 Cheol Young Park , Shou Matsumoto

Many biological processes involve numerous coupled degrees of freedom, yet free-energy estimation is often restricted to one-dimensional profiles to mitigate the high computational cost of multidimensional sampling. In this work, we extend…

Statistical Mechanics · Physics 2026-02-12 Daniel Nagel , Tristan Bereau

This paper presents a meta-theory of the usage of the free energy principle (FEP) and examines its scope in the modelling of physical systems. We consider the so-called `map-territory fallacy' and the fallacious reification of model…

History and Philosophy of Physics · Physics 2025-06-24 Maxwell J D Ramstead , Dalton A R Sakthivadivel , Karl J Friston

The impact of leading collective electronic fluctuations on a free energy of a prototype 1D model for molecular systems is considered within the recently developed Fluctuating Local Field (FLF) approach. The FLF method is a non-perturbative…

Strongly Correlated Electrons · Physics 2022-01-14 Yana S. Lyakhova , Evgeny A. Stepanov , Alexey N. Rubtsov

Umbrella sampling is an efficient method for the calculation of free energy changes of a system along well-defined reaction coordinates. However, when multiple parallel channels along the reaction coordinate or hidden barriers in directions…

Methodology · Statistics 2015-06-16 Mingjun Yang , Lijiang Yang , Yiqin Gao , Hao Hu