ABSTRACT: BACKGROUND: A large number of studies have been carried out to obtain amino acid propensities for ?-helices and ?-sheets. The obtained propensities for ?-helices are consistent with each other, and the pair-wise correlation coefficient is frequently high. On the other hand, the ?-sheet propensities obtained by several studies differed significantly, indicating that the context significantly affects ?-sheet propensity. RESULTS: We calculated amino acid propensities for ?-helices and ?-sheets for 39 and 24 protein folds, respectively, and addressed whether they correlate with the fold. The propensities were also calculated for exposed and buried sites, respectively. Results showed that ?-helix propensities do not differ significantly by fold, but ?-sheet propensities are diverse and depend on the fold. The propensities calculated for exposed sites and buried sites are similar for ?-helix, but such is not the case for the ?-sheet propensities. We also found some fold dependence on amino acid frequency in ?-strands. Folds with a high Ser, Thr and Asn content at exposed sites in ?-strands tend to have a low Leu, Ile, Glu, Lys and Arg content (correlation coefficient = -0.90) and to have flat ?-sheets. At buried sites in ?-strands, the content of Tyr, Trp, Gln and Ser correlates negatively with the content of Val, Ile and Leu (correlation coefficient = -0.93). "All-?" proteins tend to have a higher content of Tyr, Trp, Gln and Ser, whereas "?/?" proteins tend to have a higher content of Val, Ile and Leu. CONCLUSIONS: The ?-helix propensities are similar for all folds and for exposed and buried residues. However, ?-sheet propensities calculated for exposed residues differ from those for buried residues, indicating that the exposed-residue fraction is one of the major factors governing amino acid composition in ?-strands. Furthermore, the correlations we detected suggest that amino acid composition is related to folding properties such as the twist of a ?-strand or association between two ? sheets.
