ETNA: Equilibrium transitions network and Arrhenius equation for extracting folding kinetics from REMD simulations
Title | ETNA: Equilibrium transitions network and Arrhenius equation for extracting folding kinetics from REMD simulations |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Muff S., Caflisch A. |
Journal | The Journal of Physical Chemistry B |
Volume | 113 |
Issue | 10 |
Pagination | 3218-3226 |
Date Published | 2009 Mar 12 |
Type of Article | Research Article |
Keywords | Antioxidants, 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. |
DOI | 10.1021/jp807261h |
pubindex | 0108 |
Alternate Journal | J. Phys. Chem. B |
PubMed ID | 19231819 |