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.
BT - The Journal of Physical Chemistry B C1 - 0108 DA - 2009 Mar 12 DO - 10.1021/jp807261h IS - 10 J2 - J. Phys. Chem. B LA - eng M3 - Research Article N2 -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.
PY - 2009 SP - 3218 EP - 3226 T2 - The Journal of Physical Chemistry B TI - ETNA: Equilibrium transitions network and Arrhenius equation for extracting folding kinetics from REMD simulations VL - 113 SN - 1520-6106 ER -