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

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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.

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Cellular and Molecular Biology, Faculty of Science, Azarbaijan University of Tarbiat Moallem, P.O. Box 53714-161, Tabriz, Iran

    Faramarz Mehrnejad & Mohammad Mehdi Ghahremanpour

  2. Department of Physics, Faculty of Science, Azad University of Bonab, Bonab, Iran

    Mahmoud Khadem-Maaref

  3. Department of Microbiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Farahnoosh Doustdar

Authors
  1. Faramarz Mehrnejad
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  2. Mahmoud Khadem-Maaref
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  3. Mohammad Mehdi Ghahremanpour
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  4. Farahnoosh Doustdar
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Corresponding author

Correspondence to Faramarz Mehrnejad.

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Mehrnejad, F., Khadem-Maaref, M., Ghahremanpour, M.M. et al. Mechanisms of amphipathic helical peptide denaturation by guanidinium chloride and urea: a molecular dynamics simulation study. J Comput Aided Mol Des 24, 829–841 (2010). https://doi.org/10.1007/s10822-010-9377-x

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  • DOI: https://doi.org/10.1007/s10822-010-9377-x

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