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Journal of Computer-Aided Molecular Design

, Volume 24, Issue 10, pp 829–841 | Cite as

Mechanisms of amphipathic helical peptide denaturation by guanidinium chloride and urea: a molecular dynamics simulation study

  • Faramarz Mehrnejad
  • Mahmoud Khadem-Maaref
  • Mohammad Mehdi Ghahremanpour
  • Farahnoosh Doustdar
Article

Abstract

Urea and GdmCl are widely used to denature proteins at high concentrations. Here, we used MD simulations to study the denaturation mechanisms of helical peptide in different concentrations of GdmCl and urea. It was found that the helical structure of the peptide in water simulation is disappeared after 5 ns while the helicity of the peptide is disappeared after 70 ns in 2 M urea and 25 ns in 1 M GdmCl. Surprisingly, this result shows that the helical structure in low concentration of denaturants is remained more with respect to that solvated in water. The present work strongly suggests that urea interact more preferentially to non-polar and aromatic side chains in 2 M urea; therefore, hydrophobic residues are in more favorable environment in 2 M urea. Our results also reveal that the hydrogen bonds between urea and the backbone is the dominant mechanism by which the peptide is destabilized in high concentration of urea. In 1 M and 2 M GdmCl, GdmCl molecules tend to engage in transient stacking interactions with aromatics and hydrophobic planar side chains that lead to displacement of water from the hydration surface, providing more favorable environment for them. This shows that accumulation of GdmCl around hydrophobic surfaces in 1 M and 2 M GdmCl solutions prevents proper solvation of the peptide at the beginning. In high GdmCl concentrations, water solvate the peptide better than 1 M and 2 M GdmCl. Therefore, our results strongly suggest that hydrogen bonds between water and the peptide are important factors in the destabilization of peptide in GdmCl solutions.

Keywords

Osmolytes Alpha helical peptide Urea Guanidinium chloride Hydrogen bond Hydrophobic interaction 

Notes

Acknowledgments

The support of the Azarbaijan University of Tarbiat Moallem is gratefully acknowledged.

Supplementary material

10822_2010_9377_MOESM1_ESM.doc (300 kb)
Supplementary material 1 (DOC 300 kb)

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Faramarz Mehrnejad
    • 1
  • Mahmoud Khadem-Maaref
    • 2
  • Mohammad Mehdi Ghahremanpour
    • 1
  • Farahnoosh Doustdar
    • 3
  1. 1.Department of Cellular and Molecular Biology, Faculty of ScienceAzarbaijan University of Tarbiat MoallemTabrizIran
  2. 2.Department of Physics, Faculty of ScienceAzad University of BonabBonabIran
  3. 3.Department of Microbiology, Faculty of MedicineShahid Beheshti University of Medical SciencesTehranIran

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