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We present an approach that extends the theory of targeted free energy perturbation (TFEP) to calculate free energy differences and free energy surfaces at an accurate quantum mechanical level of theory from a cheaper reference potential.…

Computational Physics · Physics 2021-11-15 Andrea Rizzi , Paolo Carloni , Michele Parrinello

The Targeted Free Energy Perturbation (TFEP) method aims to overcome the time-consuming and computer-intensive stratification process of standard methods for estimating the free energy difference between two states. To achieve this, TFEP…

Chemical Physics · Physics 2023-02-24 Soo Jung Lee , Amr H. Mahmoud , Markus A. Lill

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

Free energy perturbation (FEP) is frequently used to evaluate the free energy change of a biological process, e.g. the drug binding free energy or the ligand solvation free energy. Due to the sampling inefficiency, FEP is often employed…

Chemical Physics · Physics 2017-01-31 Ying-Chih Chiang , Frank Otto

Targeted free energy perturbation uses an invertible mapping to promote configuration space overlap and the convergence of free energy estimates. However, developing suitable mappings can be challenging. Wirnsberger et al. (2020)…

Statistical Mechanics · Physics 2024-01-02 Soohaeng Yoo Willow , Lulu Kang , David D. L. Minh

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 Free-Energy-Principle (FEP) is an influential and controversial theory which postulates a deep and powerful connection between the stochastic thermodynamics of self-organization and learning through variational inference. Specifically,…

Artificial Intelligence · Computer Science 2021-10-05 Beren Millidge , Anil Seth , Christopher L Buckley

A generalization of the free energy perturbation identity is derived, and a computational strategy based on this result is presented. A simple example illustrates the efficiency gains that can be achieved with this method.

Statistical Mechanics · Physics 2009-11-07 C. Jarzynski

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 Free Energy Principle (FEP) states that under suitable conditions of weak coupling, random dynamical systems with sufficient degrees of freedom will behave so as to minimize an upper bound, formalized as a variational free energy, on…

Quantum Physics · Physics 2022-07-21 Chris Fields , Karl Friston , James F. Glazebrook , Michael Levin

The free energy principle (FEP) is a mathematical framework that describes how biological systems self-organize and survive in their environment. This principle provides insights on multiple scales, from high-level behavioral and cognitive…

Neurons and Cognition · Quantitative Biology 2021-03-24 David Kappel , Christian Tetzlaff

Reinforcement Learning (RL) requires a large amount of exploration especially in sparse-reward settings. Imitation Learning (IL) can learn from expert demonstrations without exploration, but it never exceeds the expert's performance and is…

Machine Learning · Computer Science 2021-07-27 Ryoya Ogishima , Izumi Karino , Yasuo Kuniyoshi

The 'free energy principle' (FEP) has been suggested to provide a unified theory of the brain, integrating data and theory relating to action, perception, and learning. The theory and implementation of the FEP combines insights from…

Neurons and Cognition · Quantitative Biology 2017-05-26 Christopher L. Buckley , Chang Sub Kim , Simon McGregor , Anil K. Seth

In QM/MM indirect free energy simulation, QM/MM corrections can be obtained from integration of partial derivatives of alchemical Hamiltonians or from perturbation-based estimators including free energy perturbation (FEP) and acceptance…

Chemical Physics · Physics 2018-10-05 Xiaohui Wang , Zhaoxi Sun

Ensembling is now recognized as an effective approach for increasing the predictive performance and calibration of deep networks. We introduce a new approach, Parameter Ensembling by Perturbation (PEP), that constructs an ensemble of…

Machine Learning · Computer Science 2020-10-27 Alireza Mehrtash , Purang Abolmaesumi , Polina Golland , Tina Kapur , Demian Wassermann , William M. Wells

Deep learning has revolutionised artificial intelligence (AI) by enabling automatic feature extraction and function approximation from raw data. However, it faces challenges such as a lack of out-of-distribution generalisation, catastrophic…

Neural and Evolutionary Computing · Computer Science 2025-02-14 Mehran H. Bazargani , Szymon Urbas , Karl Friston

Finding optimal solutions to combinatorial optimization problems is pivotal in both scientific and technological domains, within academic research and industrial applications. A considerable amount of effort has been invested in the…

Statistical Mechanics · Physics 2024-12-13 Zi-Song Shen , Feng Pan , Yao Wang , Yi-Ding Men , Wen-Biao Xu , Man-Hong Yung , Pan Zhang

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

We introduce and analyze free energy landscapes defined by associating to any point inside the sphere a free energy calculated on a thin spherical band around it, using many orthogonal replicas. This allows us to reinterpret, rigorously…

Probability · Mathematics 2023-05-23 Eliran Subag

Navigation in the natural world is a feat of adaptive inference, where biological organisms maintain goal-directed behaviour despite noisy and incomplete sensory streams. Central to this ability is the Free Energy Principle (FEP), which…

Robotics · Computer Science 2026-03-06 Maytus Piriyajitakonkij , Rishabh Dev Yadav , Mingfei Sun , Mengmi Zhang , Wei Pan
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