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Sample size derivation is a crucial element of the planning phase of any confirmatory trial. A sample size is typically derived based on constraints on the maximal acceptable type I error rate and a minimal desired power. Here, power…

Existing optimal estimators of nonequilibrium path-ensemble averages are shown to fall within the framework of extended bridge sampling. Using this framework, we derive a general minimal-variance estimator that can combine nonequilibrium…

Statistical Mechanics · Physics 2011-12-06 David D. L. Minh , John D. Chodera

We introduce and analyze free energy landscapes defined by associating to any point inside the sphere a free energy calculated on a thin spherical band around it, using many orthogonal replicas. This allows us to reinterpret, rigorously…

Probability · Mathematics 2023-05-23 Eliran Subag

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

Response-adaptive randomization (RAR) can increase participant benefit in clinical trials, but also complicates statistical analysis. The burn-in period (a non-adaptive initial stage) is commonly used to mitigate this disadvantage, yet…

Methodology · Statistics 2025-10-14 Edwin Y. N. Tang , Stef Baas , Daniel Kaddaj , Lukas Pin , David S. Robertson , Sofía S. Villar

Current theories of heteropolymers are inherently macrpscopic, but are applied to folding proteins which are only mesoscopic. In these theories, one computes the averaged free energy over sequences, always assuming that it is self-averaging…

Soft Condensed Matter · Physics 2009-11-07 Jeffrey Chuang , Alexander Yu. Grosberg , Mehran Kardar

Thermodynamic integration (TI) offers a rigorous method for estimating free-energy differences by integrating over a sequence of interpolating conformational ensembles. However, TI calculations are computationally expensive and typically…

Statistical Mechanics · Physics 2024-12-04 Bálint Máté , François Fleuret , Tristan Bereau

For many important problems the quantity of interest is an unknown function of the parameters, which is a random vector with known statistics. Since the dependence of the output on this random vector is unknown, the challenge is to identify…

Machine Learning · Statistics 2021-04-28 Themistoklis P. Sapsis

We study the transition probabilities of a two-point measurement on a quantum system, initially prepared in a thermal state. We find two independent constraints on the difference between transition probabilities when the system is prepared…

Mesoscale and Nanoscale Physics · Physics 2025-05-20 Ludovico Tesser , Matteo Acciai , Christian Spånslätt , Inès Safi , Janine Splettstoesser

This paper is committed to investigate an extension of the classical adaptive biasing force method, which is used to compute the free energy related to the Boltzmann-Gibbs measure and a reaction coordinate function. The issue of this…

Probability · Mathematics 2017-11-08 Houssam AlRachid , Tony Lelievre

The free energy landscapes of several fundamental processes are characterized by high barriers separating long-lived metastable states. In order to explore these type of landscapes enhanced sampling methods are used. While many such methods…

Chemical Physics · Physics 2019-04-12 Jayashrita Debnath , Michele Invernizzi , Michele Parrinello

We present a method for computing free-energy differences using thermodynamic integration with a neural network potential that interpolates between two target Hamiltonians. The interpolation is defined at the sample distribution level, and…

Statistical Mechanics · Physics 2025-03-26 Bálint Máté , François Fleuret , Tristan Bereau

Free-energy-based adaptive biasing methods, such as Metadynamics, the Adaptive Biasing Force (ABF) and their variants, are enhanced sampling algorithms widely used in molecular simulations. Although their efficiency has been empirically…

Probability · Mathematics 2026-01-29 Tony Lelièvre , Xuyang Lin , Pierre Monmarché

We present a detailed comparison of computational efficiency and precision for several free energy difference ($\Delta F$) methods. The analysis includes both equilibrium and non-equilibrium approaches, and distinguishes between…

Biological Physics · Physics 2009-11-11 F. Marty Ytreberg , Robert H. Swendsen , Daniel M. Zuckerman

A novel overlap histogramming method based on Dual-Topology Hamiltonian-Replica-Exchange simulation technique is presented to efficiently calculate relative free energy difference in rough energy landscape, in which multiple conformers…

Chemical Physics · Physics 2013-06-24 Donghong Min , Hongzhi Li , Guohui Li , Ryan Bitter-Putzer , Wei Yang

This paper presents an advancement to an approach for model-independent surrogate-based optimization with adaptive batch sampling, known as Adaptive Model Refinement (AMR). While the original AMR method provides unique decisions with…

Optimization and Control · Mathematics 2019-06-04 Payam Ghassemi , Sumeet Sanjay Lulekar , Souma Chowdhury

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

We perform a series of cosmological simulations using Enzo, an Eulerian adaptive-mesh refinement, N-body + hydrodynamical code, applied to study the warm/hot intergalactic medium. The WHIM may be an important component of the baryons…

Cosmology and Nongalactic Astrophysics · Physics 2015-05-19 Britton D. Smith , Eric J. Hallman , J. Michael Shull , Brian W. O'Shea

Umbrella sampling efficiently yields equilibrium averages that depend on exploring rare states of a model by biasing simulations to windows of coordinate values and then combining the resulting data with physical weighting. Here, we…

Statistical Mechanics · Physics 2016-09-21 Erik Thiede , Brian Van Koten , Jonathan Weare , Aaron R. Dinner

General analytic energy bounds are derived for N-boson systems governed by ultrarelativistic Hamiltonians of the form H = sum_{i=1}^N||p_i|| + sum_{1=i<j}^N V(r_{ij}), where V(r) is a static attractive pair potential. It is proved that a…

Mathematical Physics · Physics 2011-11-10 Richard L. Hall , Wolfgang Lucha
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