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We present an efficient method for the calculation of free energy landscapes. Our approach involves a history dependent bias potential which is evaluated on a grid. The corresponding free energy landscape is constructed via a histogram…

Computational Physics · Physics 2011-03-03 Jens Smiatek , Andreas Heuer

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 present a method to explore the free energy landscapes of chemical reactions with post-transition-state bifurcations using an enhanced sampling method based on well-tempered metadynamics. Obviating the need for computationally expensive…

Chemical Physics · Physics 2023-04-18 Juno Nam , YounJoon Jung

Accurate phase diagram calculation from molecular dynamics requires systematic treatment and convergence of statistical averages. In this work we propose a Gaussian process regression based framework for reconstructing the free energy…

Computational Physics · Physics 2021-11-02 V. Ladygin , I. Beniya , E. Makarov , A. Shapeev

We propose an adiabatic reweighting algorithm for computing the free energy along an external parameter from adaptive molecular dynamics simulations. The adaptive bias is estimated using Bayes identity and information from all the sampled…

Statistical Mechanics · Physics 2014-04-08 Lingling Cao , Gabriel Stoltz , Tony Lelièvre , Mihai-Cosmin Marinica , Manuel Athènes

The equilibrium free energy landscape of off-lattice model heteropolymers as a function of an internal coordinate, namely the end-to-end distance, is reconstructed from out-of-equilibrium steered molecular dynamics data. This task is…

Statistical Mechanics · Physics 2008-09-17 Stefano Luccioli , Alberto Imparato , Alessandro Torcini

Many enhanced sampling techniques rely on the identification of a number of collective variables that describe all the slow modes of the system. By constructing a bias potential in this reduced space one is then able to sample efficiently…

Computational Physics · Physics 2019-03-05 Michele Invernizzi , Michele Parrinello

Describing the complex landscape of infinite-dimensional free energy is generally a challenging problem. This difficulty arises from the existence of numerous minimizers and, consequently, a vast number of saddle points. These factors make…

Soft Condensed Matter · Physics 2025-07-15 Keiichiro Kagawa , Takeshi Watanabe , Yasumasa Nishiura

The present paper proposes an adaptive biasing potential for the computation of free energy landscapes. It is motivated by statistical learning arguments and unifies the tasks of biasing the molecular dynamics to escape free energy wells…

Mathematical Physics · Physics 2018-03-05 I. Bilionis , P. S. Koutsourelakis

We present a method for determining the free energy dependence on a selected number of collective variables using an adaptive bias. The formalism provides a unified description which has metadynamics and canonical sampling as limiting…

Statistical Mechanics · Physics 2008-03-31 Alessandro Barducci , Giovanni Bussi , Michele Parrinello

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

Many biological processes involve numerous coupled degrees of freedom, yet free-energy estimation is often restricted to one-dimensional profiles to mitigate the high computational cost of multidimensional sampling. In this work, we extend…

Statistical Mechanics · Physics 2026-02-12 Daniel Nagel , Tristan Bereau

Ab initio metadynamics enables extracting free-energy landscapes having the accuracy of first principles electronic structure methods. We introduce an interface between the PLUMED code that computes free-energy landscapes and…

Materials Science · Physics 2022-04-20 Daniel Sucerquia , Cristian Parra , Pilar Cossio , Olga Lopez-Acevedo

We investigate the kinetics and the free energy landscape of the crystallization of hard spheres from a supersaturated metastable liquid though direct simulations and forward flux sampling. In this first paper, we describe and test two…

Soft Condensed Matter · Physics 2018-08-17 David Richard , Thomas Speck

The equilibrium free energy landscape of an off-lattice model protein as a function of an internal (reaction) coordinate is reconstructed from out-of-equilibrium mechanical unfolding manipulations. This task is accomplished via two…

Statistical Mechanics · Physics 2007-10-17 Alberto Imparato , Stefano Luccioli , Alessandro Torcini

Metadynamics is an enhanced sampling method of great popularity, based on the on-the-fly construction of a bias potential that is function of a selected number of collective variables. We propose here a change in perspective that shifts the…

Computational Physics · Physics 2020-03-24 Michele Invernizzi , Michele Parrinello

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

The solid-liquid interface free energy \gamma sl is a key parameter controlling nucleation and growth during solidification and other phenomena. There are intrinsic difficulties in obtaining accurate experimental values, and the previous…

Materials Science · Physics 2010-05-20 Stefano Angioletti-Uberti , Michele Ceriotti , Mike W. Finnis , Peter D. Lee

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 describe a method to explore the configurational phase space of chemical systems. It is based on the nested sampling algorithm recently proposed by Skilling [Skilling J. (2004) In AIP Conference Proceedings, vol. 735, p. 395.; Skilling…

Statistical Mechanics · Physics 2010-07-08 Livia B. Pártay , Albert P. Bartók , Gábor Csányi
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