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

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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.

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

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Acknowledgments

The authors thank Prof. H.J.C. Berendsen (University of Groningen) for providing us with the GROMACS programs.

This work was supported by grants 31000324, 61271378 and 30970561 from the National Natural Science Foundation of China and grants 2009ZRA14027 and 2009ZRA14028 from the Shandong Province Natural Science Foundation.

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Authors and Affiliations

  1. Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Dezhou, 253023, China

    Zanxia Cao, Liling Zhao, Haiyan Li & Jihua Wang

  2. Department of Physics, Dezhou University, Dezhou, 253023, China

    Zanxia Cao, Liling Zhao, Haiyan Li & Jihua Wang

  3. Department of Computer Science and Technology, Dezhou University, Dezhou, 253023, China

    Lei Liu

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  1. Zanxia Cao
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  2. Lei Liu
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  3. Liling Zhao
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Correspondence to Jihua Wang.

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Fig. S1a–b

Initial structures of a the unbound and b the Cu2+-bound α-syn12 peptide. (DOC 84 kb)

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Cao, Z., Liu, L., Zhao, L. et al. Comparison of the structural characteristics of Cu2+-bound and unbound α-syn12 peptide obtained in simulations using different force fields. J Mol Model 19, 1237–1250 (2013). https://doi.org/10.1007/s00894-012-1664-0

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  • DOI: https://doi.org/10.1007/s00894-012-1664-0

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