A quantum mechanical study of the intrinsic helix‐forming tendency of α‐aminoisobutyric acid and dehydroalanine residues

A quantum mechanical study to compare the ability of α‐aminoisobutyric acid (Aib), de‐hydroalanine (ΔAla), and alanine (Ala) residues to stabilize helical conformations has been performed. To address the study, the oligopeptides X n (X = Aib, ΔAla and Ala), where n varies from 1 to 6, were computed with the AM1 semiempirical method. The results show that the residues modified at the C α carbon atom, Aib and ΔAla, are better helical formers than Ala. Thus, a cooperative energy effect was found for both residues, and especially for ΔAla. These terms permit the understanding the different conformational behaviors between Ala and its C α ‐modified residues Aib and ΔAla. This trend is important for de novo protein design, where Aib and ΔAla must be considered useful residues in the design of synthetic helical motifs. © 1994 John Wiley & Sons, Inc.