Journal of Molecular Modeling

, Volume 19, Issue 3, pp 1237–1250

Comparison of the structural characteristics of Cu2+-bound and unbound α-syn12 peptide obtained in simulations using different force fields

Authors

  • Zanxia Cao
    • Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics
    • Department of PhysicsDezhou University
  • Lei Liu
    • Department of Computer Science and TechnologyDezhou University
  • Liling Zhao
    • Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics
    • Department of PhysicsDezhou University
  • Haiyan Li
    • Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics
    • Department of PhysicsDezhou University
    • Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics
    • Department of PhysicsDezhou University
Original Paper

DOI: 10.1007/s00894-012-1664-0

Cite this article as:
Cao, Z., Liu, L., Zhao, L. et al. J Mol Model (2013) 19: 1237. doi:10.1007/s00894-012-1664-0

Abstract

The effects of Cu2+ binding and the utilization of different force fields when modeling the structural characteristics of α-syn12 peptide were investigated. To this end, we performed extensive temperature replica exchange molecular dynamics (T-REMD) simulations on Cu2+-bound and unbound α-syn12 peptide using the GROMOS 43A1, OPLS-AA, and AMBER03 force fields. Each replica was run for 300 ns. The structural characteristics of α-syn12 peptide were studied based on backbone dihedral angle distributions, free-energy surfaces obtained with different reaction coordinates, favored conformations, the formation of different Turn structures, and the solvent exposure of the hydrophobic residues. The findings show that AMBER03 prefers to sample helical structures for the unbound α-syn12 peptide and does not sample any β-hairpin structure for the Cu2+-bound α-syn12 peptide. In contrast, the central structure of the major conformational clusters for the Cu2+-bound and unbound α-syn12 peptide according to simulations performed using the GROMOS 43A1 and OPLS-AA force fields is a β-hairpin with Turn9-6. Cu2+ can also promote the formation of the β-hairpin and increase the solvent exposure of hydrophobic residues, which promotes the aggregation of α-syn12 peptide. This study can help us to understand the mechanisms through which Cu2+ participates in the fibrillation of α-syn12 peptide at the atomic level, which in turn represents a step towards elucidating the nosogenesis of Parkinson’s disease.

https://static-content.springer.com/image/art%3A10.1007%2Fs00894-012-1664-0/MediaObjects/894_2012_1664_Figa_HTML.gif
Figure

The representative structures of Cu2+-bound and unbound α-syn12 peptide using three different force fields

Keywords

Cu2+-bound α-syn12 peptideEffects of Cu2+Effects of different force fieldsTemperature replica exchangeFree-energy surfaceSolvent exposure of hydrophobic residues

Supplementary material

894_2012_1664_MOESM1_ESM.doc (84 kb)
Fig. S1a–bInitial structures of a the unbound and b the Cu2+-bound α-syn12 peptide. (DOC 84 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2012