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Related papers: Multi-Layer Free Energy Perturbation

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Free energy perturbation (FEP) was proposed by Zwanzig more than six decades ago as a method to estimate free energy differences, and has since inspired a huge body of related methods that use it as an integral building block. Being an…

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

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

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

Free energy perturbation (FEP) is considered the gold-standard simulation method for estimating small molecule binding affinity, a quantity of vital importance to drug discovery. The accuracy of FEP critically depends on an accurate model…

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 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

Calculating relative free energies is a topic of substantial interest and has many applications including solvation and binding free energies, which are used in computational drug discovery. However, there remain the challenges of accuracy,…

Chemical Physics · Physics 2016-09-28 Asaf Farhi , Bipin Singh

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

Many enhanced sampling techniques rely on the identification of a number of collective variables that describe all the slow modes of the system. By constructing a bias potential in this reduced space one is then able to sample efficiently…

Computational Physics · Physics 2019-03-05 Michele Invernizzi , Michele Parrinello

In this thesis we examine methodologies for determining free energy differences (FEDs) of phases via Monte Carlo simulation. We identify and address three generic issues that arise in FED calculations; the choice of representation, the…

Statistical Mechanics · Physics 2009-09-29 Arjun R. Acharya

The use of free energy perturbation (FEP) methods to study protein-ligand complexes is one of the most important tools in structure-based drug design. Because FEP methods typically rely on force fields, they may suffer from force field…

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

Sampling the free energy surface, namely, the distribution of collective variables (CVs), is a crucial problem in statistical physics, as it underpins a better understanding of chemical reactions and conformational transitions. Traditional…

Machine Learning · Computer Science 2026-05-04 Zichen Liu , Tiejun Li

Predicting the binding affinity between small molecules and target macromolecules while combining both speed and accuracy, is a cornerstone of modern computational drug discovery which is critical for accelerating therapeutic development.…

The free energy principle (FEP) from neuroscience provides a framework called active inference for the joint estimation and control of state space systems, subjected to colored noise. However, the active inference community has been…

Systems and Control · Electrical Eng. & Systems 2022-04-06 Ajith Anil Meera , Martijn Wisse

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

Many methods to accelerate sampling of molecular configurations are based on the idea that temperature can be used to accelerate rare transitions. These methods typically compute equilibrium properties at a target temperature using…

Chemical Physics · Physics 2023-11-30 Kangxin Liu , Grant M. Rotskoff , Eric Vanden-Eijnden , Glen M. Hocky

The minimum free-energy path (MFEP) is the most probable route of the nucleation process on the multidimensional free-energy surface. In this study, the phase-field equation is used as a mathematical tool to deduce the minimum free-energy…

Materials Science · Physics 2015-05-13 Masao Iwamatsu
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