Abstract
The classical picture of H-bonds has evolved considerably. In contrast to earlier expectations, C-H⋯O H-bonds are now known to be prevalent in both small organic and large biological systems. However, there are few reports on the energetic contribution of C-H⋯O H-bonds in protein or polypeptide systems and we do not know whether such interactions are stabilizing. Here we investigate C-H⋯O H-bonding interactions between Phe and Glu side chains by determining their effects on the helicity of model α-helical peptides using a combination of CD and NMR spectroscopy. The results suggest that Glu/Phe C-H⋯O H-bonding interactions stabilize helical structure, but only in the orientation Glu→Phe (N→C). Each Glu→Phe (N→C) interaction can contribute approximately -0.5 kcal mol-1 to the stability of helical peptide. In the reverse orientation, Phe→Glu (N→C) appears to contribute negligibly. pH titrations provide further evidence for the existence of C-H⋯O H-bonds. The C-H⋯O H-bonding interactions in these peptides are insensitive to the screening effect of added neutral salt. Our results provide quantitative energetic information on C-H⋯O H-bonds that should be useful for empirical force-field calibration.
Original language | English (US) |
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Pages (from-to) | 267-279 |
Number of pages | 13 |
Journal | Biophysical Chemistry |
Volume | 101 |
Issue number | 102 |
DOIs | |
State | Published - Dec 10 2002 |
Keywords
- C-H⋯O H-bonds
- Energetics
- Free energy
- α-Helix
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Organic Chemistry