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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

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

Calculating relative free energies is a topic of substantial interest and has many applications including solvation and binding free energies, which are used in computational drug discovery. However, there remain the challenges of accuracy,…

Chemical Physics · Physics 2016-09-28 Asaf Farhi , Bipin Singh

State-of-the-art simulations of high-energy nuclear collisions rely on hybrid setups, involving in particular a pre-equilibrium stage to let the system evolve from a far-from-equilibrium initial condition towards a near-equilibrated state…

Nuclear Theory · Physics 2024-10-31 Nicolas Borghini , Renata Krupczak , Hendrik Roch

In this work we propose a new algorithm for the computation of statistical equilibrium quantities on a cubic lattice when both an energy and a statistical temperature are involved. We demonstrate that the pivot algorithm used in situations…

Statistical Mechanics · Physics 2021-06-15 Pavel Bělík , Eric Bibelnieks , Robert Laskowski , Aleksandr Lukanen , Douglas P. Dokken

The qualitative solvent- and temperature-dependent conformational behavior of a peptide in the proximity of solid substrates with different adsorption properties is investigated by means of a simple lattice model. The resulting pseudophase…

Soft Condensed Matter · Physics 2007-10-25 Michael Bachmann , Wolfhard Janke

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

We present results of molecular simulations of a model protein whose hydrophobic collapse proceeds as a cascade of downhill transitions between distinct intermediate states. Different intermediates are stabilized by means of appropriate…

Soft Condensed Matter · Physics 2009-11-13 Natalia A. Denesyuk , John D. Weeks

When a system is driven out of equilibrium by a time-dependent protocol that modifies the Hamiltonian, it follows a nonequilibrium path. Samples of these paths can be used in nonequilibrium work theorems to estimate equilibrium quantities,…

Statistical Mechanics · Physics 2009-05-29 David D. L. Minh

We introduce a new procedure to construct weight factors, which flatten the probability density of the overlap with respect to some pre-defined reference configuration. This allows one to overcome free energy barriers in the overlap…

Statistical Mechanics · Physics 2009-11-10 B. A. Berg , H. Noguchi , Y. Okamoto

Free energies play a central role in characterising the behaviour of chemical systems and are among the most important quantities that can be calculated by molecular dynamics simulations. Solvation free energies in various organic solvents,…

Chemical Physics · Physics 2026-02-11 J. Harry Moore , Daniel J. Cole , Gabor Csanyi

Ensuring a satisfactory statistical convergence of anharmonic thermodynamic properties requires sampling of many atomic configurations, however the methods to obtain those necessarily produce correlated samples, thereby reducing the…

Statistical Mechanics · Physics 2022-06-07 Erki Metsanurk

The effectiveness of a new algorithm, parallel tempering, is studied for numerical simulations of biological molecules. These molecules suffer from a rough energy landscape. The resulting slowing down in numerical simulations is overcome by…

Chemical Physics · Physics 2009-10-30 Ulrich H. E. Hansmann

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

Let Delta F be the free energy difference between two equilibrium states of a system. An established method of numerically computing Delta F involves a single, long ``switching simulation'', during which the system is driven reversibly from…

Statistical Mechanics · Physics 2009-11-07 D. A. Hendrix , C. Jarzynski

The computational study of conformational transitions in RNA and proteins with atomistic molecular dynamics often requires suitable enhanced sampling techniques. We here introduce a novel method where concurrent metadynamics are integrated…

Computational Physics · Physics 2015-09-01 Alejandro Gil-Ley , Giovanni Bussi

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

We present a simulation protocol that allows for efficient sampling of the degrees of freedom of a solute in explicit solvent. The protocol involves using a non-equilibrium umbrella sampling method, in this case the recently developed…

Chemical Physics · Physics 2010-03-16 Volodymyr Babin , Celeste Sagui

Among lattice configurations of densely packed hard ellipses, Monte Carlo simulations are used to identify the so-called parallel and diagonal lattices as the two favourable states. The free energies of these two states are computed for…

Soft Condensed Matter · Physics 2024-03-27 Susanne Wagner , Gerhard Kahl , Roman Melnyk , Andrij Baumketner

Preparing Gibbs states, which describe systems in equilibrium at finite temperature, is of great importance, particularly at low temperatures. In this work, we propose a new method -- TEPID-ADAPT -- that prepares the thermal Gibbs state of…

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