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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Bibliographic Details
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
Description
Summary: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.