STRUCTURAL CLASSIFICATION OF ALPHA-BETA-BETA AND BETA-BETA-ALPHA SUPERSECONDARY STRUCTURE UNITS IN PROTEINS

We present a fully automatic structural classification of superseconda ry structure units, consisting of two hydrogen-bonded beta strands, pr eceded or followed by an alpha helix. The classification is performed on the spatial arrangement of the secondary structure elements, irresp ective of the length and conformation of the intervening loops. The si milarity of the arrangements is estimated by a structure alignment pro cedure that uses as similarity measure the root mean square deviation of superimposed backbone atoms. Applied to a set of 141 well-resolved nonhomologous protein structures, the classification yields 11 familie s of recurrent arrangements. In addition, fragments that are structura lly intermediate between the families are found; they reveal the conti nuity of the classification. The analysis of the families shows that t he alpha helix and beta hairpin axes can adopt virtually all relative orientations, with, however, some preferable orientations; moreover, a ccording to the orientation, preferences in the left/right handedness of the alpha-beta connection are observed. These preferences can be ex plained by favorable side by side packing of the alpha helix and the b eta hairpin, local interactions in the region of the alpha-beta connec tion or stabilizing environments in the parent protein. Furthermore, f old recognition procedures and structure prediction algorithms coupled to database-derived potentials suggest that the preferable nature of these arrangements does not imply their intrinsic stability. They usua lly accommodate a large number of sequences, of which only a subset is predicted to stabilize the motif. The moths predicted as stable could correspond to nuclei formed at the very beginning of the folding proc ess. (C) 1998 Wiley-Liss, Inc.