Header

UZH-Logo

Maintenance Infos

ETNA: Equilibrium Transitions Network and Arrhenius Equation for Extracting Folding Kinetics from REMD Simulations


Muff, S; Caflisch, A (2009). ETNA: Equilibrium Transitions Network and Arrhenius Equation for Extracting Folding Kinetics from REMD Simulations. Journal of Physical Chemistry. B, 113(10):3218-3226.

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 beta-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 mus at the melting temperature of 330 K to about 8 mus at 286 K) as well as transition times from individual non-native basins to the native state.

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 beta-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 mus at the melting temperature of 330 K to about 8 mus at 286 K) as well as transition times from individual non-native basins to the native state.

Statistics

Citations

23 citations in Web of Science®
23 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 06 Apr 2009
0 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:March 2009
Deposited On:06 Apr 2009 15:57
Last Modified:05 Apr 2016 13:12
Publisher:American Chemical Society
ISSN:1520-5207
Publisher DOI:https://doi.org/10.1021/jp807261h
PubMed ID:19231819

Download

Preview Icon on Download
Content: Accepted Version
Filetype: PDF - Registered users only
Size: 1MB
View at publisher