ETNA: Equilibrium transitions network and Arrhenius equation for extracting folding kinetics from REMD simulations

TitleETNA: Equilibrium transitions network and Arrhenius equation for extracting folding kinetics from REMD simulations
Publication TypeJournal Article
Year of Publication2009
AuthorsMuff S., Caflisch A.
JournalThe Journal of Physical Chemistry B
Volume113
Issue10
Pagination3218-3226
Date Published2009 Mar 12
Type of ArticleResearch Article
ISSN1520-6106
KeywordsAntioxidants, Biophysics, Coloring Agents, computational biology, Computer Simulation, Electrons, Free Radical Scavengers, Free Radicals, Kinetics, Models, Chemical, Models, Molecular, Models, Theoretical, Molecular Conformation, Polyenes, Thermodynamics
Abstract

It is difficult to investigate folding kinetics by conventional atomistic simulations of proteins. The replica exchange molecular dynamics (REMD) simulation technique enhances conformational sampling at the expenses of reduced kinetic information, which in REMD is directly available only for very short time scales. Here, we propose a procedure for obtaining kinetic data from REMD by making use of the equilibrium transitions network (ETN) sampled at the temperature of interest. This information is supplemented by mean folding times extracted from ETNs at higher REMD temperatures and scaled according to the Arrhenius equation. The procedure is applied to a three-stranded antiparallel β-sheet peptide which has a very heterogeneous denatured state with a broad entropic basin and several enthalpic traps. Despite the complexity of the system and the REMD exchange time of only 0.1 ns, the procedure is able to estimate folding times (ranging from about 0.1 μs at the melting temperature of 330 K to about 8 μs at 286 K) as well as transition times from individual non-native basins to the native state.

DOI10.1021/jp807261h
pubindex

0108

Alternate JournalJ. Phys. Chem. B
PubMed ID19231819
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