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Title: Accelerated weight histogram method for exploring free energy landscapes

Abstract

Calculating free energies is an important and notoriously difficult task for molecular simulations. The rapid increase in computational power has made it possible to probe increasingly complex systems, yet extracting accurate free energies from these simulations remains a major challenge. Fully exploring the free energy landscape of, say, a biological macromolecule typically requires sampling large conformational changes and slow transitions. Often, the only feasible way to study such a system is to simulate it using an enhanced sampling method. The accelerated weight histogram (AWH) method is a new, efficient extended ensemble sampling technique which adaptively biases the simulation to promote exploration of the free energy landscape. The AWH method uses a probability weight histogram which allows for efficient free energy updates and results in an easy discretization procedure. A major advantage of the method is its general formulation, making it a powerful platform for developing further extensions and analyzing its relation to already existing methods. Here, we demonstrate its efficiency and general applicability by calculating the potential of mean force along a reaction coordinate for both a single dimension and multiple dimensions. We make use of a non-uniform, free energy dependent target distribution in reaction coordinate space so that computationalmore » efforts are not wasted on physically irrelevant regions. We present numerical results for molecular dynamics simulations of lithium acetate in solution and chignolin, a 10-residue long peptide that folds into a β-hairpin. We further present practical guidelines for setting up and running an AWH simulation.« less

Authors:
; ;  [1]
  1. Department of Theoretical Physics and Swedish e-Science Research Center, KTH Royal Institute of Technology, 10691 Stockholm (Sweden)
Publication Date:
OSTI Identifier:
22419913
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Chemical Physics; Journal Volume: 141; Journal Issue: 4; Other Information: (c) 2014 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; ACETATES; EFFICIENCY; FREE ENERGY; MOLECULAR DYNAMICS METHOD; PEPTIDES; SIMULATION; SOLUTIONS

Citation Formats

Lindahl, V., Lidmar, J., and Hess, B. Accelerated weight histogram method for exploring free energy landscapes. United States: N. p., 2014. Web. doi:10.1063/1.4890371.
Lindahl, V., Lidmar, J., & Hess, B. Accelerated weight histogram method for exploring free energy landscapes. United States. doi:10.1063/1.4890371.
Lindahl, V., Lidmar, J., and Hess, B. Mon . "Accelerated weight histogram method for exploring free energy landscapes". United States. doi:10.1063/1.4890371.
@article{osti_22419913,
title = {Accelerated weight histogram method for exploring free energy landscapes},
author = {Lindahl, V. and Lidmar, J. and Hess, B.},
abstractNote = {Calculating free energies is an important and notoriously difficult task for molecular simulations. The rapid increase in computational power has made it possible to probe increasingly complex systems, yet extracting accurate free energies from these simulations remains a major challenge. Fully exploring the free energy landscape of, say, a biological macromolecule typically requires sampling large conformational changes and slow transitions. Often, the only feasible way to study such a system is to simulate it using an enhanced sampling method. The accelerated weight histogram (AWH) method is a new, efficient extended ensemble sampling technique which adaptively biases the simulation to promote exploration of the free energy landscape. The AWH method uses a probability weight histogram which allows for efficient free energy updates and results in an easy discretization procedure. A major advantage of the method is its general formulation, making it a powerful platform for developing further extensions and analyzing its relation to already existing methods. Here, we demonstrate its efficiency and general applicability by calculating the potential of mean force along a reaction coordinate for both a single dimension and multiple dimensions. We make use of a non-uniform, free energy dependent target distribution in reaction coordinate space so that computational efforts are not wasted on physically irrelevant regions. We present numerical results for molecular dynamics simulations of lithium acetate in solution and chignolin, a 10-residue long peptide that folds into a β-hairpin. We further present practical guidelines for setting up and running an AWH simulation.},
doi = {10.1063/1.4890371},
journal = {Journal of Chemical Physics},
number = 4,
volume = 141,
place = {United States},
year = {Mon Jul 28 00:00:00 EDT 2014},
month = {Mon Jul 28 00:00:00 EDT 2014}
}
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