title: An experiment-based algorithm for predicting the partitioning of unfolded peptides into phosphatidylcholine bilayer interfaces.
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.
authors.affiliation: Department of Materials Science and Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Kalina
authors.initials: K
authors.lastname: Hristova
authors.forename: Stephen H
authors.initials: SH
authors.lastname: White
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008051:Lipid Bilayers; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D009842:Oligopeptides; D010713:Phosphatidylcholines