A QUANTUM-MECHANICAL STUDY OF THE INTRINSIC HELIX-FORMING TENDENCY OF ALPHA-AMINOISOBUTYRIC-ACID AND DEHYDROALANINE RESIDUES

A quantum mechanical study to compare the ability of alpha-aminoisobutyric acid (Aib), dehydroalanine (Delta Ala), and alanine (Ala) residues to stabilize helical conformations has been performed. To address the study, the oligopeptides X(n) (X = Aib, Delta Ala 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-a carbon atom, Aib and Delta Ala, are better helical formers than Ala. Thus, a cooperative energy effect was found for both residues, and especially for Delta Ala. These terms permit the understanding the different conformational behaviors between Ala and its C-a-modified residues Aib and Delta Ala. This trend is important for de novo protein design, where Aib and Delta Ala must be considered useful residues in the design of synthetic helical motifs. (C) 1994 John Wiley & Sons, Inc.