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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 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

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

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 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 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

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

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

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

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

Transition path sampling is a method for estimating the rates of rare events in molecular systems based on the gradual transformation of a path distribution containing a small fraction of reactive trajectories into a biased distribution in…

Statistical Mechanics · Physics 2015-10-28 Pierre Terrier , Mihai-Cosmin Marinica , Manuel Athènes

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

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

Our ability to calculate rates of biochemical processes using molecular dynamics simulations is severely limited by the fact that the time scales for reactions, or changes in conformational state, scale exponentially with the relevant…

Chemical Physics · Physics 2024-03-19 Nicodemo Mazzaferro , Subarna Sasmal , Pilar Cossio , Glen M. Hocky

Atomistic simulations provide valuable insights into the physical processes governing material behavior. However, their applicability is fundamentally constrained by the limited time scales accessible to brute-force simulations. This…

Computational Physics · Physics 2026-02-16 Michael Kim , Wei Cai

We propose an efficient, accurate and reliable simulation scheme for the stochastic-alpha-beta-rho (SABR) model. The two challenges of the SABR simulation lie in sampling (i) integrated variance conditional on terminal volatility and (ii)…

Computational Finance · Quantitative Finance 2025-10-06 Jaehyuk Choi , Lilian Hu , Yue Kuen Kwok

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…

Stochastic systems often exhibit multiple viable metastable states that are long-lived. Over very long timescales, fluctuations may push the system to transition between them, drastically changing its macroscopic configuration. In realistic…

Statistical Mechanics · Physics 2023-04-14 Tobias Grafke , Alessandro Laio
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