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We present a new estimator for computing free energy differences and thermodynamic expectations as well as their uncertainties from samples obtained from multiple equilibrium states via either simulation or experiment. The estimator, which…

Computational Physics · Physics 2011-12-06 Michael R. Shirts , John D. Chodera

The multistate Bennett Acceptance Ratio is provably the lowest variance unbiased estimator of both free energies and ensemble averages, and has a number of important advantages over previous methods, such as WHAM. Despite its advantages,…

Statistical Mechanics · Physics 2017-12-20 Michael R. Shirts

Free energy calculations based on atomistic Hamiltonians provide microscopic insight into the thermodynamic driving forces of biophysical or condensed matter systems. Many approaches use intermediate Hamiltonians interpolating between the…

Computational Physics · Physics 2021-12-08 Martin Reinhardt , Helmut Grubmüller

Multiple sampling strategies commonly used in molecular dynamics, such as umbrella sampling and alchemical free energy methods, involve sampling from multiple thermodynamic states. Commonly, the data are then recombined to construct…

Statistical Mechanics · Physics 2023-06-14 Xiang Sherry Li , Brian Van Koten , Aaron R. Dinner , Erik H. Thiede

Free energy of crystal phases is commonly evaluated by thermodynamic integration (TDI) along a reversible path that involves an external potential. A persistent problem in this method is that a significant hysteresis is observed due to…

Materials Science · Physics 2010-02-27 Pankaj A. Apte

The dynamics of molecules are governed by rare event transitions between long-lived (metastable) states. To explore these transitions efficiently, many enhanced sampling protocols have been introduced that involve using simulations with…

Chemical Physics · Physics 2022-09-30 Maaike M. Galama , Hao Wu , Andreas Krämer , Mohsen Sadeghi , Frank Noé

Free energy calculations based on atomistic Hamiltonians and sampling are key to a first principles understanding of biomolecular processes, material properties, and macromolecular chemistry. Here, we generalize the Free Energy Perturbation…

Computational Physics · Physics 2023-07-19 Martin Reinhardt , Helmut Grubmüller

Free energy difference calculations based on atomistic simulations generally improve in accuracy when sampling from a sequence of intermediate equilibrium thermodynamic states that bridge the configuration space between two states of…

Computational Physics · Physics 2020-10-21 Martin Reinhardt , Helmut Grubmüller

Free energy profile (FE Profile) is an essential quantity for the estimation of reaction rate and the validation of reaction mechanism. For chemical reactions in condensed phase or enzymatic reactions, the computation of FE profile at ab…

Computational Physics · Physics 2018-11-15 Pengfei Li , Xiangyu Jia , Xiaoliang Pan , Yihan Shao , Ye Mei

Free energies are fundamental quantities governing phase behavior and thermodynamic stability in polymer systems, yet their accurate computation often requires extensive simulations and post-processing techniques such as the Bennett…

Soft Condensed Matter · Physics 2026-03-19 Ian Chen , Alfredo Alexander-Katz

We show how thermodynamic properties of molecular models can be computed over a large, multidimensional parameter space by combining multistate reweighting analysis with a linear basis function approach. This approach reduces the…

Chemical Physics · Physics 2016-05-18 Levi N. Naden , Michael R. Shirts

Because of their multimodality, mixture posterior distributions are difficult to sample with standard Markov chain Monte Carlo (MCMC) methods. We propose a strategy to enhance the sampling of MCMC in this context, using a biasing procedure…

Computation · Statistics 2011-04-19 Nicolas Chopin , Tony Lelievre , Gabriel Stoltz

Computing the equilibrium properties of complex systems, such as free energy differences, is often hampered by rare events in the dynamics. Enhanced sampling methods may be used in order to speed up sampling by, for example, using high…

Computational Physics · Physics 2015-02-11 Antonia S. J. S. Mey , Hao Wu , Frank Noé

We introduce a method to compute the reweighted path ensemble by combining transition interface sampling simulations conditioned on different collective variables. The approach is based on the Multistate Bennett Acceptance Ratio (MBAR)…

Statistical Mechanics · Physics 2026-04-20 Rik S. Breebaart , Peter G. Bolhuis

The conformational free energy landscape of a system is a fundamental thermodynamic quantity of importance particularly in the study of soft matter and biological systems, in which the entropic contributions play a dominant role. While…

Biological Physics · Physics 2015-10-13 N. Ramakrishnan , Richard W. Tourdot , Ravi Radhakrishnan

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

This paper applies the Bayesian Model Averaging (BMA) statistical ensemble technique to estimate small molecule solvation free energies. There is a wide range of methods available for predicting solvation free energies, ranging from…

Biomolecules · Quantitative Biology 2016-12-16 Luke J. Gosink , Christopher C. Overall , Sarah M. Reehl , Paul D. Whitney , David L. Mobley , Nathan A. Baker

In modern computer experiment applications, one often encounters the situation where various models of a physical system are considered, each implemented as a simulator on a computer. An important question in such a setting is determining…

Methodology · Statistics 2023-05-08 John C. Yannotty , Thomas J. Santner , Richard J. Furnstahl , Matthew T. Pratola

Accurately inferring the state of a quantum device from the results of measurements is a crucial task in building quantum information processing hardware. The predominant state estimation procedure, maximum likelihood estimation (MLE),…

Quantum Physics · Physics 2010-05-04 Robin Blume-Kohout

A powerful and well-established tool for free-energy estimation is Bennett's acceptance ratio method. Central properties of this estimator, which employs samples of work values of a forward and its time reversed process, are known: for…

Statistical Mechanics · Physics 2009-09-16 Aljoscha Maria Hahn , Holger Then
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