A bias-exchange approach to protein folding

By suitably extending a recent approach [G. Bussi et al, J Am Chem Soc 2006, 128, 13435] we introduce a powerful methodology that allows the parallel reconstruction of the free energy of a system in a virtually unlimited number of variables. Multiple metadynamics simulations of the same system at th...

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Main Authors: Piana, Stefano, Laio, A.
Format: Journal Article
Published: American Chemical Society 2007
Subjects:
Online Access:http://pubs.acs.org/cgi-bin/article.cgi/jpcbfk/2007/111/i17/pdf/jp067873l.pdf
http://hdl.handle.net/20.500.11937/15651
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author Piana, Stefano
Laio, A.
author_facet Piana, Stefano
Laio, A.
author_sort Piana, Stefano
building Curtin Institutional Repository
collection Online Access
description By suitably extending a recent approach [G. Bussi et al, J Am Chem Soc 2006, 128, 13435] we introduce a powerful methodology that allows the parallel reconstruction of the free energy of a system in a virtually unlimited number of variables. Multiple metadynamics simulations of the same system at the same temperature are performed, biasing each replica with a time-dependent potential constructed in a different set of collective variables. Exchanges between the bias potentials in the different variables are periodically allowed according to a replica exchange scheme. Due to the efficaciously multidimensional nature of the bias the method allows exploring complex free energy landscapes with high efficiency. The usefulness of the method is demonstrated by performing an atomistic simulation in explicit solvent of the folding of a Triptophane cage miniprotein. It is shown that the folding free energy landscape can be fully characterized starting from an extended conformation using only 40 ns of simulation on 8 replicas.
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spelling curtin-20.500.11937-156512017-10-02T02:26:56Z A bias-exchange approach to protein folding Piana, Stefano Laio, A. Trp-cage protein folding molecular dynamics simulation free energy replica exchange Metadynamics By suitably extending a recent approach [G. Bussi et al, J Am Chem Soc 2006, 128, 13435] we introduce a powerful methodology that allows the parallel reconstruction of the free energy of a system in a virtually unlimited number of variables. Multiple metadynamics simulations of the same system at the same temperature are performed, biasing each replica with a time-dependent potential constructed in a different set of collective variables. Exchanges between the bias potentials in the different variables are periodically allowed according to a replica exchange scheme. Due to the efficaciously multidimensional nature of the bias the method allows exploring complex free energy landscapes with high efficiency. The usefulness of the method is demonstrated by performing an atomistic simulation in explicit solvent of the folding of a Triptophane cage miniprotein. It is shown that the folding free energy landscape can be fully characterized starting from an extended conformation using only 40 ns of simulation on 8 replicas. 2007 Journal Article http://hdl.handle.net/20.500.11937/15651 http://pubs.acs.org/cgi-bin/article.cgi/jpcbfk/2007/111/i17/pdf/jp067873l.pdf http://purl.org/au-research/grants/arc/DP0558938 American Chemical Society fulltext
spellingShingle Trp-cage
protein folding
molecular dynamics simulation
free energy
replica exchange
Metadynamics
Piana, Stefano
Laio, A.
A bias-exchange approach to protein folding
title A bias-exchange approach to protein folding
title_full A bias-exchange approach to protein folding
title_fullStr A bias-exchange approach to protein folding
title_full_unstemmed A bias-exchange approach to protein folding
title_short A bias-exchange approach to protein folding
title_sort bias-exchange approach to protein folding
topic Trp-cage
protein folding
molecular dynamics simulation
free energy
replica exchange
Metadynamics
url http://pubs.acs.org/cgi-bin/article.cgi/jpcbfk/2007/111/i17/pdf/jp067873l.pdf
http://pubs.acs.org/cgi-bin/article.cgi/jpcbfk/2007/111/i17/pdf/jp067873l.pdf
http://hdl.handle.net/20.500.11937/15651