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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

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

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

Pre-calculated libraries of molecular fragment configurations have previously been used as a basis for both equilibrium sampling (via "library-based Monte Carlo") and for obtaining absolute free energies using a polymer-growth formalism.…

Quantitative Methods · Quantitative Biology 2018-12-26 Steven Lettieri , Artem B. Mamonov , Daniel M. Zuckerman

We adapted existing polymer growth strategies for equilibrium sampling of peptides described by modern atomistic forcefields with implicit solvent. The main novel feature of our approach is the use of pre-calculated statistical libraries of…

Biological Physics · Physics 2010-03-04 A. B. Mamonov , X. Zhang , D. M. Zuckerman

In this work, I propose a statistical mechanical framework, for the evaluation of the free energy in molecular systems, by "deleting" all the molecules in a "single" step. The approach can be considered as the statistical mechanics…

Statistical Mechanics · Physics 2011-08-16 Georgios C. Boulougouris

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…

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

We devise automated workflows for the calculation of Helmholtz and Gibbs free energies and their temperature and pressure dependence and provide the corresponding computational tools. We employ non-equilibrium thermodynamics for evaluating…

Materials Science · Physics 2021-10-13 Sarath Menon , Yury Lysogorskiy , Jutta Rogal , Ralf Drautz

We propose a simple estimator that allows to calculate the absolute value of a system's partition function from a finite sampling of its canonical ensemble. The estimator utilizes a volume correction term to compensate the effect that the…

Statistical Mechanics · Physics 2024-09-05 Ying-Chih Chiang , Frank Otto , Jonathan W. Essex

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

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…

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

Predictions of relative stabilities of (competing) molecular crystals are of great technological relevance, most notably for the pharmaceutical industry. However, they present a long-standing challenge for modeling, as often minuscule free…

Materials Science · Physics 2022-05-25 Venkat Kapil , Edgar A Engel

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…

We propose a numerical technique to compute the equilibrium free energy of glasses that cannot be prepared quasi-reversibly. For such systems, standard techniques for estimating the free energy by extrapolation, cannot be used. Instead, we…

Statistical Mechanics · Physics 2021-01-04 H. A. Vinutha , Daan Frenkel

Fast and accurate evaluation of free energy has broad applications from drug design to material engineering. Computing the absolute free energy is of particular interest since it allows the assessment of the relative stability between…

Statistical Mechanics · Physics 2021-02-24 Xinqiang Ding , Bin Zhang

As minimal cells or protocells are dramatically simpler than modern unicells it is possible to quantitatively estimate free energy changes for every process in the lifecycle of a protocell and compare these with estimates of the free energy…

This work addresses the question of whether it is possible to define simple pair-wise interaction terms to approximate free energies of proteins or polymers. Rather than ask how reliable a potential of mean force is, one can ask how…

Soft Condensed Matter · Physics 2009-10-31 Dirk Reith , Thomas Huber , Florian Mueller-Plathe , Andrew E. Torda
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