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In this contribution I critically revise the alchemical reversible approach in the context of the statistical mechanics theory of non covalent bonding in drug receptor systems. I show that most of the pitfalls and entanglements for the…

Biomolecules · Quantitative Biology 2016-06-29 Piero Procacci

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

A promising method for calculating free energy differences Delta F is to generate non-equilibrium data via ``fast-growth'' simulations or experiments -- and then use Jarzynski's equality. However, a difficulty with using Jarzynski's…

Computational Physics · Physics 2007-05-23 F. Marty Ytreberg , Daniel M. Zuckerman

We propose a proof of convergence of an adaptive method used in molecular dynamics to compute free energy profiles. Mathematically, it amounts to studying the long-time behavior of a stochastic process which satisfies a non-linear…

Analysis of PDEs · Mathematics 2007-06-13 Tony Lelievre , Felix Otto , Mathias Rousset , Gabriel Stoltz

A vast array of phenomena, ranging from chemical reactions to phase transformations, are analysed in terms of a free energy surface defined with respect to a single or multiple order parameters. Enhanced sampling methods are typically used,…

Statistical Mechanics · Physics 2023-04-26 Yagyik Goswami , Srikanth Sastry

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

We present a calculation of the change of free energy of a solid surface upon bending of the solid. It is based on extracting the surface stress through a molecular dynamics simulation of a bent slab by using a generalized stress theorem…

Materials Science · Physics 2007-05-23 U. Tartaglino , D. Passerone , E. Tosatti , F. Di Tolla

Ground state structures found in nature are in many cases of high symmetry. But structure prediction methods typically render only a small fraction of high symmetry structures. Especially for large crystalline unit cells there are many low…

Computational Physics · Physics 2022-09-13 Hannes Huber , Martin Sommer , Moritz Gubler , Stefan Goedecker

Existing adaptive bias techniques, which seek to estimate free energies and physical properties from molecular simulations, are limited by their reliance on fixed kernels or basis sets which hinder their ability to efficiently conform to…

Statistical Mechanics · Physics 2018-04-04 Hythem Sidky , Jonathan K. Whitmer

We introduce a simple enhanced sampling approach for the calculation of free energy differences and barriers along a one-dimensional reaction coordinate. First, a small number of short nonequilibrium simulations are carried out along the…

Chemical Physics · Physics 2021-11-03 Kristof M. Bal

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

Our paper deals with inferring simulator-based statistical models given some observed data. A simulator-based model is a parametrized mechanism which specifies how data are generated. It is thus also referred to as generative model. We…

Machine Learning · Statistics 2016-01-01 Michael U. Gutmann , Jukka Corander

We develop a novel and general framework for reduced-bias $M$-estimation from asymptotically unbiased estimating functions. The framework relies on an empirical approximation of the bias by a function of derivatives of estimating function…

Methodology · Statistics 2023-08-11 Ioannis Kosmidis , Nicola Lunardon

Free energy landscapes encode the kinetics, intermediates, and transition states that govern molecular processes and are thus a key target of single biomolecule research. Typical approaches to deriving optimal, error-minimizing,…

Biological Physics · Physics 2025-11-25 Oliver Cheng , Zosia Adamska , Michael P. Brenner , Megan C. Engel

We consider large-scale studies in which it is of interest to test a very large number of hypotheses, and then to estimate the effect sizes corresponding to the rejected hypotheses. For instance, this setting arises in the analysis of gene…

Methodology · Statistics 2015-03-31 Kean Ming Tan , Noah Simon , Daniela Witten

We present a new method to evaluate vibrational free energies of atomic systems without a priori specification of an interatomic potential. Our model-agnostic approach leverages descriptors, high-dimensional feature vectors of atomic…

Materials Science · Physics 2025-03-05 Thomas D Swinburne , Clovis Lapointe , Mihai-Cosmin Marinica

An important challenge in statistical analysis lies in controlling the bias of estimators due to the ever-increasing data size and model complexity. Approximate numerical methods and data features like censoring and misclassification often…

Statistics Theory · Mathematics 2020-11-17 Stéphane Guerrier , Mucyo Karemera , Samuel Orso , Maria-Pia Victoria-Feser , Yuming Zhang

Coarse graining techniques play an essential role in accelerating molecular simulations of systems with large length and time scales. Theoretically grounded bottom-up models are appealing due to their thermodynamic consistency with the…

Computational Physics · Physics 2022-11-01 Blake R. Duschatko , Jonathan Vandermause , Nicola Molinari , Boris Kozinsky

Signal processing of uniformly spaced data from stationary stochastic processes with missing samples is investigated. Besides randomly and independently occurring outliers also correlated data gaps are investigated. Non-parametric…

Signal Processing · Electrical Eng. & Systems 2023-04-28 Nils Damaschke , Volker Kühn , Holger Nobach

Computationally-guided material discovery is being increasingly employed using a descriptor-based screening through the calculation of a few properties of interest. A precise understanding of the uncertainty associated with first principles…

Materials Science · Physics 2016-08-22 Zeeshan Ahmad , Venkatasubramanian Viswanathan