Pairwise coupling in an Arg-Phe-Met triplet stabilizes alpha-helical peptide via shared rotamer preferences.
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.
Iqbalsyah
Teuku M
TM
Faculty of Life Sciences, Jackson's Mill, The University of Manchester, P.O. Box 88, Sackville Street, Manchester M60 1QD, UK.
Doig
Andrew J
AJ
D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D008715:Methionine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D010455:Peptides; C019529:polyalanine; D010649:Phenylalanine; D001120:Arginine; D008715:Methionine