Pairwise coupling in an Arg-Phe-Met triplet stabilizes alpha-helical peptide via shared rotamer preferences

J Am Chem Soc. 2005 Apr 13;127(14):5002-3. doi: 10.1021/ja043446e.

Abstract

The hydrophobic Arg-Phe and Phe-Met side chain interactions stabilize the alpha-helix by -0.29 and -0.59 kcal/mol, respectively, when placed i, i + 4 in an alanine-based peptide. When both interactions are present simultaneously, however, they stabilize the helix by an additional -0.75 kcal/mol, nearly as much as the sum of its parts. We attribute this coupling to a shared rotamer preference, as the central Phe is t in both bonds. The energetic cost of restricting the Phe residue into a t conformation is only paid once in the triplet, rather than twice when the interactions are separate. Coupling is thus demonstrated to have large effects on protein stability.

MeSH terms

  • Amino Acid Sequence
  • Arginine / chemistry
  • Methionine / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemistry*
  • Phenylalanine / chemistry
  • Protein Structure, Secondary
  • Thermodynamics

Substances

  • Peptides
  • polyalanine
  • Phenylalanine
  • Arginine
  • Methionine