Conformational preferences of oligopeptides rich in α‐aminoisobutyric acid. II. A model for the 310/α‐helix transition with composition and sequence sensitivity

Abstract

The analysis of the factors that control the helical folding of Aib‐rich peptides is extended to include sensitivity to sequence patterns, and in particular the presence of contiguous non‐Aib α‐mono‐alkylated residues. The distinct hydrogen‐bonding network of the 3₁₀−helix, as contrasted with that of the competing α‐helical structure, is explicitly incorporated into a theoretical model for the 3₁₀−helix/α‐helix equilibrium constant for a given peptide. Finite length effects and the “extra” intrahelical hydrogen bond of the 3₁₀ form are expressed naturally as a result of this loop analysis. This semiempirical model captures all the established features of existing empirical rules for helical conformational transitions in Aib‐rich sequences, as well as the recently detected helical transition induced solely by sequence permutation.