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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

We propose a discrete transition-based reweighting analysis method (dTRAM) for analyzing configuration-space-discretized simulation trajectories produced at different thermodynamic states (temperatures, Hamiltonians, etc.) dTRAM provides…

Data Analysis, Statistics and Probability · Physics 2015-06-23 Hao Wu , Antonia S. J. S. Mey , Edina Rosta , Frank Noé

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

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

When studying high-dimensional dynamical systems such as macromolecules, quantum systems and polymers, a prime concern is the identification of the most probable states and their stationary probabilities or free energies. Often, these…

Data Analysis, Statistics and Probability · Physics 2013-01-01 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

Atomistic modelling of phase transitions, chemical reactions, or other rare events that involve overcoming high free energy barriers usually entails prohibitively long simulation times. Introducing a bias potential as a function of an…

Computational Physics · Physics 2019-11-06 Federico Giberti , Bingqing Cheng , Gareth Aneurin Tribello , Michele Ceriotti

The histogram reweighting technique, widely used to analyze Monte Carlo data, is shown to be applicable to dynamic properties obtained from Molecular Dynamics simulations. The theory presented here is based on the fact that the correlation…

Statistical Mechanics · Physics 2009-11-11 Carlos Nieto-Draghi , Javier Perez-Pellitero , Josep Bonet Avalos

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

Direct simulation of biomolecular dynamics in thermal equilibrium is challenging due to the metastable nature of conformation dynamics and the computational cost of molecular dynamics. Biased or enhanced sampling methods may improve the…

Chemical Physics · Physics 2015-06-12 Benjamin Trendelkamp-Schroer , Frank Noe

We propose a new method for the determination of the weight factor for the simulated tempering method. In this method a short replica-exchange simulation is performed and the simulated tempering weight factor is obtained by the…

Statistical Mechanics · Physics 2009-10-31 A. Mitsutake , Y. Okamoto

The multistate Bennett acceptance ratio (MBAR) method is a prevalent approach for computing free energies of thermodynamic states. In this work, we introduce BayesMBAR, a Bayesian generalization of the MBAR method. By integrating…

Chemical Physics · Physics 2024-02-16 Xinqiang Ding

Markov chain Monte Carlo methods are primarily used for sampling from a given probability distribution and estimating multi-dimensional integrals based on the information contained in the generated samples. Whenever it is possible, more…

Statistical Mechanics · Physics 2017-05-22 Manuel Athènes , Pierre Terrier

Simulations with an adaptive time-dependent bias, such as metadynamics, enable an efficient exploration of the conformational space of a system. However, the dynamic information of the system is altered by the bias. With infrequent…

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

We present a generic reweighting method for nonequilibrium Markov processes. With nonequilibrium Monte Carlo simulations at a single temperature, one calculates the time evolution of physical quantities at different temperatures, which…

Statistical Mechanics · Physics 2009-11-10 Hwee Kuan Lee , Yutaka Okabe

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

General circulation models (GCMs) are essential tools for climate studies. Such climate models may have varying accuracy across the input domain, but no model is uniformly best. One can improve climate model prediction performance by…

Methodology · Statistics 2026-01-27 John C. Yannotty , Thomas J. Santner , Bo Li , Matthew T. Pratola

We derive the optimal estimates of the free energies of an arbitrary number of thermodynamic states from nonequilibrium work measurements; the work data are collected from forward and reverse switching processes and obey a fluctuation…

Statistical Mechanics · Physics 2009-11-11 Paul Maragakis , Martin Spichty , Martin Karplus

We propose a method for efficient simulations in extended ensembles, useful, e.g., for the study of problems with complex energy landscapes and for free energy calculations. The main difficulty in such simulations is the estimation of the a…

Statistical Mechanics · Physics 2012-05-29 Jack Lidmar
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