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The weighted ensemble (WE) simulation strategy provides unbiased sampling of non-equilibrium processes, such as molecular folding or binding, but the extraction of rate constants relies on characterizing steady state behavior.…

Statistical Mechanics · Physics 2020-10-02 Jeremy Copperman , Daniel Zuckerman

We extend the weighted ensemble (WE) path sampling method to perform rigorous statistical sampling for systems at steady state. The straightforward steady-state implementation of WE is directly practical for simple landscapes, but not when…

Biological Physics · Physics 2015-05-14 Divesh Bhatt , Bin W. Zhang , Daniel M. Zuckerman

To directly simulate rare events using atomistic molecular dynamics is a significant challenge in computational biophysics. Well-established enhanced-sampling techniques do exist to obtain the thermodynamic functions for such systems. But…

Statistical Mechanics · Physics 2020-07-21 Dhiman Ray , Ioan Andricioaei

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 apply the "weighted ensemble" (WE) simulation strategy, previously employed in the context of molecular dynamics simulations, to a series of systems-biology models that range in complexity from one-dimensional to a system with 354…

Molecular Networks · Quantitative Biology 2015-03-11 Rory M. Donovan , Andrew J. Sedgewick , James R. Faeder , Daniel M. Zuckerman

Equilibrium formally can be represented as an ensemble of uncoupled systems undergoing unbiased dynamics in which detailed balance is maintained. Many non-equilibrium processes can be described by suitable subsets of the equilibrium…

In the last decade, advances in molecular dynamics (MD) and Markov State Model (MSM) methodologies have made possible accurate and efficient estimation of kinetic rates and reactive pathways for complex biomolecular dynamics occurring on…

Biomolecules · Quantitative Biology 2020-01-29 Hongbin Wan , Vincent A. Voelz

Weighted ensemble (WE) is an enhanced path-sampling method that is conceptually simple, widely applicable, and statistically exact. In a WE simulation, an ensemble of trajectories is periodically pruned or replicated to enhance sampling of…

We provide an algorithm based on weighted-ensemble (WE) methods, to accurately sample systems at steady state. Applying our method to different one- and two-dimensional models, we succeed to calculate steady state probabilities of order…

Statistical Mechanics · Physics 2015-06-15 Justus A. Kromer , Lutz Schimansky-Geier , Raul Toral

The weighted ensemble (WE) method, an enhanced sampling approach based on periodically replicating and pruning trajectories in a set of parallel simulations, has grown increasingly popular for computational biochemistry problems, due in…

Computational Physics · Physics 2023-06-23 D. Aristoff , J. Copperman , G. Simpson , R. J. Webber , D. M. Zuckerman

A significant challenge in molecular dynamics (MD) simulations is ensuring that sampled configurations converge to the equilibrium or nonequilibrium stationary distribution of interest. Lack of convergence constrains the estimation of free…

Computational Physics · Physics 2026-04-03 Sagar Kania , Robert J. Webber , Gideon Simpson , David Aristoff , Daniel M. Zuckerman

Molecular simulations can provide microscopic insight into the physical and chemical driving forces of complex molecular processes. Despite continued advancement of simulation methodology, model errors may lead to inconsistencies between…

Chemical Physics · Physics 2016-02-12 Joseph F. Rudzinski , Kurt Kremer , Tristan Bereau

We present a form of stratified MCMC algorithm built with non-reversible stochastic dynamics in mind. It can also be viewed as a generalization of the exact milestoning method, or form of NEUS. We prove convergence of the method under…

Probability · Mathematics 2022-02-21 Gabriel Earle , Jonathan Mattingly

Markov State Models (MSM) are widely used to elucidate dynamic properties of molecular systems from unbiased Molecular Dynamics (MD). However, the implementation of reweighting schemes for MSMs to analyze biased simulations, for example…

Chemical Physics · Physics 2020-11-26 Stefanie Kieninger , Luca Donati , Bettina G. Keller

The rapid evolution of molecular dynamics (MD) methods, including machine-learned dynamics, has outpaced the development of standardized tools for method validation. Objective comparison between simulation approaches is often hindered by…

We study optimization for losses that admit a variance-mean scale-mixture representation. Under this representation, each EM iteration is a weighted least squares update in which latent variables determine observation and parameter weights;…

Computation · Statistics 2026-02-17 Nick Polson , Vadim Sokolov

We give a mathematical framework for weighted ensemble (WE) sampling, a binning and resampling technique for efficiently computing probabilities in molecular dynamics. We prove that WE sampling is unbiased in a very general setting that…

Numerical Analysis · Mathematics 2018-10-17 David Aristoff

Parameters of the mathematical model describing many practical dynamical systems are prone to vary due to aging or renewal, wear and tear, as well as changes in environmental or service conditions. These variabilities will adversely affect…

Systems and Control · Electrical Eng. & Systems 2022-07-13 Hang Geng , Mulugeta A. Haile , Huazhen Fang

The efficient calculation of rare-event kinetics in complex dynamical systems, such as the rate and pathways of ligand dissociation from a protein, is a generally unsolved problem. Markov state models can systematically integrate ensembles…

Chemical Physics · Physics 2016-02-03 Benjamin Trendelkamp-Schroer , Frank Noe

The approximation of data is a fundamental challenge encountered in various fields, including computer-aided geometric design, the numerical solution of partial differential equations, or the design of curves and surfaces. Numerous methods…

Numerical Analysis · Mathematics 2025-01-27 Inmaculada Garcés , José M. Ramón , Juan Ruiz-Álvarez , Dionisio F. Yáñez
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