Mechanisms of amphipathic helical peptide denaturation by guanidinium chloride and urea: a molecular dynamics simulation study
- 463 Downloads
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.
KeywordsOsmolytes Alpha helical peptide Urea Guanidinium chloride Hydrogen bond Hydrophobic interaction
The support of the Azarbaijan University of Tarbiat Moallem is gratefully acknowledged.
- 4.Tanford C, Kawahara K, Lapanje S (1966) J Biol Chem 241:1921–1923Google Scholar
- 5.Greene RF, Pace CN (1974) J Biol Chem 249:5388–5393Google Scholar
- 8.Mehrnejad F, Chaparzadeh N (2008) J Biomol Struct Dyn 26:255–262Google Scholar
- 10.Shellman JA (1955) Comp Rev Trav Lab Carlsberg 29:223–229Google Scholar
- 26.Lindahl E, Hess B, van der Spoel D (2001) J Mol Mod 7:306–317Google Scholar
- 27.Van Gunsteren WF, Billeter SR, Eising AA, Hünenberger PH, Krüger P, Mark AE, Scott WRP, Tironi IG (1996) Hochschulverlag AG an der ETH Zürich, ZürichGoogle Scholar
- 28.Van der Spoel D, van Buuren AR, Apol E, Meulenhoff PJ, Tieleman DP, Sijbers ALTM, Hess B, Feenstra KA, Lindahl E, van Drunen R, Berendsen HJC (2002) Department of Biophysical Chemistry. University of Groningen, GroningenGoogle Scholar
- 55.van der Vegt NF, Lee ME, Trzesniak D, van Gunsteren WF (2006) J Phys Chem B 110:2852–12855Google Scholar