By suitably extending a recent approach [Bussi, G.; 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 ultidimensional 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 with use of only 40 ns of simulation on 8 replicas.

A bias-exchange approach to protein folding / Piana, S.; Laio, A.. - In: JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL. - ISSN 1520-6106. - 111:17(2007), pp. 4553-4559. [10.1021/jp067873l]

A bias-exchange approach to protein folding

Laio, A.
2007-01-01

Abstract

By suitably extending a recent approach [Bussi, G.; 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 ultidimensional 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 with use of only 40 ns of simulation on 8 replicas.
2007
111
17
4553
4559
Piana, S.; Laio, A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/14808
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