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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

Free energies of molecules can be calculated by quantum computations or by normal mode classical calculations. However, the first can be computationally impractical for large molecules and the second is based on the assumption of harmonic…

Chemical Physics · Physics 2016-03-23 Asaf Farhi

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

Jarzynski's identity for the free energy difference between two equilibrium states can be viewed as a special case of a more general procedure based on phase space mappings. Solving a system's equation of motion by approximate means…

Statistical Mechanics · Physics 2009-11-11 Wolfgang Lechner , Harald Oberhofer , Christoph Dellago , Phillip L. Geissler

The absolute free energy -- or partition function, equivalently -- of a molecule can be estimated computationally using a suitable reference system. Here, we demonstrate a practical method for staging such calculations by growing a molecule…

Biological Physics · Physics 2009-01-31 Xin Zhang , Artem B. Mamonov , Daniel M. Zuckerman

An expression is derived for the classical free energy difference between two configurations of a system, in terms of an ensemble of finite-time measurements of the work performed in parametrically switching from one configuration to the…

Statistical Mechanics · Physics 2009-10-28 C. Jarzynski

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

Alchemical free energy calculations are a useful tool for predicting free energy differences associated with the transfer of molecules from one environment to another. The hallmark of these methods is the use of "bridging" potential energy…

A promising method for calculating free energy differences Delta F is to generate non-equilibrium data via ``fast-growth'' simulations or experiments -- and then use Jarzynski's equality. However, a difficulty with using Jarzynski's…

Computational Physics · Physics 2007-05-23 F. Marty Ytreberg , Daniel M. Zuckerman

We propose a method, Temperature Integration, which allows an efficient calculation of free energy differences between two systems of interest, with the same degrees of freedom, which may have rough energy landscapes. The method is based on…

Statistical Mechanics · Physics 2015-06-12 Asaf Farhi , Guy Hed , Michael Bon , Nestor Caticha , Chi H Mak , Eytan Domany

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 calculations are at the heart of physics-based analyses of biochemical processes. They allow us to quantify molecular recognition mechanisms, which determine a wide range of biological phenomena from how cells send and receive…

It has recently been shown that the Helmholtz free energy difference between two equilibrium configurations of a system may be obtained from an ensemble of finite-time (nonequilibrium) measurements of the work performed in switching an…

Statistical Mechanics · Physics 2009-10-30 C. Jarzynski

Accurately computing the free energies of biological processes is a cornerstone of computer-aided drug design but it is a daunting task. The need to sample vast conformational spaces and account for entropic contributions makes the…

Free energy calculations in molecular simulations have a variety of applications including determining the strength of molecular processes such as solvation and binding. It has been recently shown that when removing the VDW and Coulomb…

Chemical Physics · Physics 2015-07-15 Asaf Farhi , Bipin Singh

Extracting equilibrium information from nonequilibrium measurements is a challenge task of great importance in understanding the thermodynamic properties of physical, chemical, and biological systems. The discovery of the Jarzynski equality…

Statistical Mechanics · Physics 2021-03-29 Geng Li , Z. C. Tu

According to the Jarzynski theorem, equilibrium free energy differences can be calculated from the statistics of work carried out during non-equilibrium transformations. Although exact, this approach can be plagued by large statistical…

Statistical Mechanics · Physics 2007-05-23 Wolfgang Lechner , Christoph Dellago

Fluctuation relations allow for the computation of equilibrium properties, like free energy, from an ensemble of non-equilibrium dynamics simulations. Computing them for quantum systems, however, can be difficult, as performing dynamic…

Quantum Physics · Physics 2021-09-07 Lindsay Bassman , Katherine Klymko , Diyi Liu , Norman M. Tubman , Wibe A. de Jong

We propose a new method to compute the free energy or enthalpy of fluids or disordered solids by computer simulation . The main idea is to construct a reference system by freezing one representative configuration, and then carry out a…

Computational Physics · Physics 2011-03-16 Friederike Schmid , Tanja Schilling

In this contribution I critically revise the alchemical reversible approach in the context of the statistical mechanics theory of non covalent bonding in drug receptor systems. I show that most of the pitfalls and entanglements for the…

Biomolecules · Quantitative Biology 2016-06-29 Piero Procacci
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