Conformational studies on peptides with proline in the right-handed alpha-helical region.

The proline residues in proteins are known to play an important structural role. Recently, the role of a proline residue in the middle of right-handed alpha-helical segments of peptides has been the focus of attention. This role seems to be particularly important in the case of membrane proteins and in the tight packing of globular proteins. In the present study the right-handed alpha-helical region of the Ala-Pro dipeptide and of polypeptides containing this group have been investigated. Crystal structures of proline-containing alpha-helices from some proteins have been analyzed and energy minimization studies on some model fragments containing Ala-Pro in the right-handed alpha-helical conformation have been carried out using flexible geometry. The present calculations indicate that the right-handed alpha-helical region of conformational space is an energetically favored region that can also accommodate Ala-Pro in longer segments of right-handed alpha-helix. This is achieved due to minor variations in some of the internal parameters. Deviations in the backbone parameters of proline in the right-handed alpha-helix lead to a kink of about 23 degrees in the helix axis. These deviations have been characterized and a set of standard values has been suggested for producing such a kink. These values can be used for model building and as starting points for further minimization studies. Previous energy minimization studies have been done using rigid geometry. This may explain why the minimum for Ala-Pro in the right-handed alpha-helical region has not been recognized thus far.