STRUCTURAL AND ENERGETIC RELATIONS BETWEEN BETA-TURNS

A systematic quantum chemical study on the structure and stability of the major types of beta-turn structures in peptides and proteins was p erformed at different levels of ab initio MO theory (MP2/6-31G, HF/6- 31G, HF/3-21G) considering model turns of the general type Ac-X-aa-Y- aa -NHCH3 with the amino acids glycine, L- and D-alanine, aminoisobuty ric acid, and L-proline. The influence of correlation effects, zero-po int vibration energies, thermal energies, and entropies on the turn fo rmation was examined. Solvent effects on the turn stabilities were est imated employing quantum chemical continuum approaches (Onsager's self -consistent reaction field and Tomasi's polarizable continuum models). The results provide insight into the geometry and stability relations between the various beta-turn subtypes. They show some characteristic deviations from the widely accepted standard rotation angles of beta turns. The stability order of the beta-turn subtypes depends strongly on the amino acid type. Thus, the replacement of L-amino acids in the two conformation-determining turn positions by D- or alpha,alpha-disub stituted amino acid residues generally increases the turn formation te ndency and can be used to favor distinct beta-turn subtypes in peptide and protein design. The beta-turn subtype preferences, depending on a mino acid structure modifications, can be well illustrated by molecula r dynamics simulations in the gas phase and in aqueous solution. (C) 1 997 by John Wiley & Sons, Inc.