Natural and synthetic peptides that contain detectable intramolecular α‐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 [θ]222 for a given peptide using the length dependence of the helix signal computed by a quantum mechanical treatment of the nπ* 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 α‐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 σ constant can account for some but not all of the available results.
ASJC Scopus subject areas
- Organic Chemistry