The folding of the amyloidogenic H1 peptide MKHMAGAAAAGAVV taken from the syrian hamster prion protein is explored in explicit aqueous solution at 300 K using long time scale all-atom molecular dynamics simulations for a total simulation time of 1.1 mu s. The system, initially modeled as an alpha-helix, preferentially adopts a beta-hairpin structure and several unfolding/refolding events are observed, yielding a very short average beta-hairpin folding time of similar to 200 ns. The long time scale accessed by our simulations and the reversibility of the folding allow to properly explore the configurational space of the peptide in solution. The free energy profile, as a function of the principal components (essential eigenvectors) of motion, describing the main conformational transitions, shows the characteristic features of a funneled landscape, with a downhill surface toward the beta-hairpin folded basin. However, the analysis of the peptide thermodynamic stability, reveals that the beta-hairpin in solution is rather unstable. These results are in good agreement with several experimental evidences, according to which the isolated H1 peptide adopts very rapidly in water beta-sheet structure, leading to amyloid fibril precipitates [Nguyen et al., Biochemistry 1995;34:4186-4192; Inouye et al., J Struct Biol 1998;122:247-255]. Moreover, in this article we also characterize the diffusion behavior in conformational space, investigating its relations with folding/unfolding conditions. (c) 2005 Wiley-Liss, Inc.

Daidone, I., Amadei, A., & Di Nola, A. (2005). Thermodynamic and kinetic characterization of a beta-hairpin peptide in solution: An extended phase space sampling by molecular dynamics simulations in explicit water. PROTEINS, 59(3), 510-518 [10.1002/prot.20427].

Thermodynamic and kinetic characterization of a beta-hairpin peptide in solution: An extended phase space sampling by molecular dynamics simulations in explicit water

AMADEI, ANDREA;
2005

Abstract

The folding of the amyloidogenic H1 peptide MKHMAGAAAAGAVV taken from the syrian hamster prion protein is explored in explicit aqueous solution at 300 K using long time scale all-atom molecular dynamics simulations for a total simulation time of 1.1 mu s. The system, initially modeled as an alpha-helix, preferentially adopts a beta-hairpin structure and several unfolding/refolding events are observed, yielding a very short average beta-hairpin folding time of similar to 200 ns. The long time scale accessed by our simulations and the reversibility of the folding allow to properly explore the configurational space of the peptide in solution. The free energy profile, as a function of the principal components (essential eigenvectors) of motion, describing the main conformational transitions, shows the characteristic features of a funneled landscape, with a downhill surface toward the beta-hairpin folded basin. However, the analysis of the peptide thermodynamic stability, reveals that the beta-hairpin in solution is rather unstable. These results are in good agreement with several experimental evidences, according to which the isolated H1 peptide adopts very rapidly in water beta-sheet structure, leading to amyloid fibril precipitates [Nguyen et al., Biochemistry 1995;34:4186-4192; Inouye et al., J Struct Biol 1998;122:247-255]. Moreover, in this article we also characterize the diffusion behavior in conformational space, investigating its relations with folding/unfolding conditions. (c) 2005 Wiley-Liss, Inc.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore CHIM/02 - Chimica Fisica
English
beta-hairpin peptide; thermodynamic characterization; molecular dynamics simulations
Daidone, I., Amadei, A., & Di Nola, A. (2005). Thermodynamic and kinetic characterization of a beta-hairpin peptide in solution: An extended phase space sampling by molecular dynamics simulations in explicit water. PROTEINS, 59(3), 510-518 [10.1002/prot.20427].
Daidone, I; Amadei, A; Di Nola, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/35251
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