An experiment-based algorithm for predicting the partitioning of unfolded peptides into phosphatidylcholine bilayer interfaces

Biochemistry. 2005 Sep 20;44(37):12614-9. doi: 10.1021/bi051193b.

Abstract

Knowing the partitioning free energy of unfolded polypeptides into membrane interfaces is necessary for understanding membrane protein stability and for designing antimicrobial and other peptides. Experiment-based whole-residue free-energy (hydropathy) scales for amino acids in unfolded peptides, derived from the partitioning of host-guest pentapeptides (Ac-WLXLL) into the interfaces of phosphatidylcholine bilayers and into n-octanol, have been determined by W. C. Wimley, S. H. White, and colleagues [(1996) Nat. Struc. Biol. 3, 842; Wimley, W. C. et al. (1996) Biochemistry 35, 5109]. These scales offer the possibility of computing absolute partitioning free energies of unfolded peptides given only their amino acid sequences. However, the scales are incomplete, because partitioning free energies of N- and C-terminal groups are missing. To complete the scales, we have measured the pH-dependent partitioning of the host-guest pentapeptide variants AcWL-X-LL-NH(2) and WL-X-LL-NH(2) (X = G or W) into palmitoyloleoylphosphatidylcholine (POPC) bilayer interfaces and n-octanol. These measurements, in combination with the earlier ones, lead to hydrophobicity scale values for protonation, deprotonation, or acetylation of the N terminus and protonation, deprotonation, or amidation of the C terminus. A surprising finding is that a charged N terminus has a much smaller effect on bilayer partitioning than a charged C terminus. We present a simple algorithm for computing the absolute partitioning free energies of unfolded peptides into the phosphatidylcholine bilayer interface.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Hydrogen-Ion Concentration
  • Kinetics
  • Lipid Bilayers
  • Models, Molecular
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry*
  • Phosphatidylcholines / chemistry*
  • Protein Denaturation
  • Protein Structure, Secondary
  • Thermodynamics

Substances

  • Lipid Bilayers
  • Oligopeptides
  • Phosphatidylcholines