THE ROLE OF CONTEXT ON ALPHA-HELIX STABILIZATION - HOST-GUEST ANALYSIS IN A MIXED BACKGROUND PEPTIDE MODEL

The helix content of a series of peptides containing single substituti ons of the 20 natural amino acids in a new designed host sequence, suc cinyl-YSEEEEKAKKAXAEEAEKKKK-NH2, has been determined using CD spectros copy. This host is related to one previously studied, in which triple amino acid substitutions were introduced into a background of Glu-Lys blocks completely lacking alanine. The resulting free energies show th at only Ala and Glu(-) prove to be helix stabilizing, while all other side chains are neutral or destabilizing. This agrees with results fro m studies of alanine-rich peptide models, but not the previous Glu-Lys block oligomers in which Leu and Met also stabilize helix. The helix propensity scale derived from the previous block oligomers correlated well with the frequencies of occurrence of different side chains in he lical sequences of proteins, whereas the values from the present serie s do not. The role of context in determining scales of helix propensit y values is discussed, and the ability of algorithms designed to predi ct helix structure from sequence is compared.