title: The helix-coil transition in heterogeneous peptides with specific side-chain interactions: theory and comparison with CD spectral data.
abstract: Natural and synthetic peptides that contain detectable intramolecular alpha-helical structure in aqueous solution have been used to evaluate the helical propensities for the common amino acids. Experimental spectroscopic data must be fit to a model of the helix-coil transition in order to determine quantitative stability constants for each amino acid. We present here a statistical mechanical description of helix formation in peptides or protein fragments that takes into account multiple internal conformations, heterogeneity in the stabilizing effects of different side chains, and specific side-chain-side-chain interactions. The model enables one to calculate values of [theta]222 for a given peptide using the length dependence of the helix signal computed by a quantum mechanical treatment of the n pi * transition that dominates the 222-nm band. In addition, the helical probability at any residue in the chain is readily computed, and should prove useful as nmr spectral data become available. The free energy of specific side-chain interactions, including ion pair formation, can be evaluated. Application of the analysis to experimental data on a pair of isomeric peptides, only one of which contains ion pairs, indicates that forming a single glutamate-lysine ion pair stabilizes the alpha-helix by 0.50 kcal/mole in 10 mM sodium ion and pH 7. A survey of the CD data measured for a variety of model peptides is presented, indicating that a single set of s values and sigma constant can account for some but not all of the available results.
authors.affiliation: Department of Chemistry, New York University, New York 10003.
authors.forename: P J
authors.initials: PJ
authors.lastname: Gans
authors.forename: P C
authors.initials: PC
authors.lastname: Lyu
authors.forename: M C
authors.initials: MC
authors.lastname: Manning
authors.forename: R W
authors.initials: RW
authors.lastname: Woody
authors.forename: N R
authors.initials: NR
authors.lastname: Kallenbach
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D008433:Mathematics; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D010455:Peptides