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The free energy functional has recently been proposed as a variational principle for bounded rational decision-making, since it instantiates a natural trade-off between utility gains and information processing costs that can be…

Machine Learning · Statistics 2012-05-18 Pedro A. Ortega , Daniel A. Braun

In the present work, we present a hybrid quantum-classical workflow aimed at improving the accuracy of alchemical free energy (AFE) predictions by incorporating configuration interaction (CI) simulations using the book-ending correction…

Chemical Physics · Physics 2025-06-27 Milana Bazayeva , Zhen Li , Danil Kaliakin , Fangchun Liang , Akhil Shajan , Susanta Das , Kenneth M. Merz

Modeling chemical reactions and complicated molecular systems has been proposed as the `killer application' of a future quantum computer. Accurate calculations of derivatives of molecular eigenenergies are essential towards this end,…

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 principles behind the computation of protein-ligand binding free energies by Monte Carlo integration are described in detail. The simulation provides gas-phase binding free energies that can be converted to aqueous energies by solvation…

Chemical Physics · Physics 2017-01-25 Matthew Clark , Jeffrey S. Wiseman

The analysis of non-equilibrium steady states of biochemical reaction networks relies on finding the configurations of fluxes and chemical potentials satisfying stoichiometric (mass balance) and thermodynamic (energy balance) constraints.…

Molecular Networks · Quantitative Biology 2011-07-13 Daniele De Martino , Matteo Figliuzzi , Andrea De Martino , Enzo Marinari

Accurate calculations of solvation free energies remain a central challenge in molecular simulations, often requiring extensive sampling and numerous alchemical intermediates to ensure sufficient overlap between phase-space distributions of…

Statistical Mechanics · Physics 2026-04-02 Maximilian Schebek , Nikolas M. Froböse , Bettina G. Keller , Jutta Rogal

Recent developments in statistical mechanics have allowed the estimation of equilibrium free energies from the statistics of work measurements during processes that drive the system out of equilibrium. Here a different class of processes is…

Statistical Mechanics · Physics 2009-11-11 Artur B. Adib

We present a new method to evaluate vibrational free energies of atomic systems without a priori specification of an interatomic potential. Our model-agnostic approach leverages descriptors, high-dimensional feature vectors of atomic…

Materials Science · Physics 2025-03-05 Thomas D Swinburne , Clovis Lapointe , Mihai-Cosmin Marinica

The accurate prediction of solvation free energy is of significant importance as it governs the behavior of solutes in solution. In this work, we apply a variety of machine learning techniques to predict and analyze the alchemical free…

Chemical Physics · Physics 2024-11-11 Mingjun Han , Yukai Zhang , Taotao Yu , Guodong Du , ChiYung Yam , Ho-Kin Tang

Accurate free-energy calculations are essential for predicting thermodynamic properties and phase stability, but existing methods are limited: phonon-based approaches neglect anharmonicity and liquids, while molecular dynamics (MD) is…

Materials Science · Physics 2025-11-19 Ekaterina Spirande , Timofei Miryashkin , Andrei Kolmakov , Alexander Shapeev

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…

Quantitative evaluations of the free energy of materials must take into account thermal and zero-point energy fluctuations. While these effects can easily be estimated within a harmonic approximation, corrections arising from the anharmonic…

Materials Science · Physics 2019-06-18 Venkat Kapil , Edgar Engel , Mariana Rossi , Michele Ceriotti

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

The surface free energy is the difference between the free energies for a system with open boundary conditions and the same system with periodic boundary conditions. We use the quantum transfer matrix formalism to express the surface free…

Statistical Mechanics · Physics 2015-06-25 Frank Göhmann , Michael Bortz , Holger Frahm

We present a family of alchemical perturbation potentials that enable the calculation of hydration free energies of small to medium-sized molecules in a concerted single alchemical coupling step instead of the commonly used sequence of two…

Quantitative Methods · Quantitative Biology 2021-02-24 Sheenam Khuttan , Solmaz Azimi , Joe Z. Wu , Emilio Gallicchio

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

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

Quantum computers have the potential to simulate chemical systems beyond the capability of classical computers. Recent developments in hybrid quantum-classical approaches enable the determinations of the ground or low energy states of…

Quantum Physics · Physics 2021-12-06 Chee-Kong Lee , Jonathan Wei Zhong Lau , Liang Shi , Leong Chuan Kwek

The Jarzynski equality (JE), which relates works of non-equilibrium trajectories to the free energy difference of the initial and final states of the non-equilibrium process, provides an efficient way to calculate free energies of systems…

Soft Condensed Matter · Physics 2016-04-20 Biao Wan , Cheng Yang , Yanting Wang , Xin Zhou