Prediction of protein helices with a derivative of the strip-of-helix hydrophobicity algorithm

The strip-of-helix hydrophobicity algorithm was devised to identify protein sequences which, when coiled as α or 3₁₀ helices, had one axial, hydrophobic strip and otherwise variably hydrophilic residues. The strip-of-helix hydrophobicity algorithm also ranked such sequences according to an index, the mean hydrophobicity of amino acids in the axial strip. This algorithm well predicted T cell-presented fragments of antigenic proteins. A derivative of this algorithm (the structural helices algorithm (SHA)) was tested for the prediction of helices in crystallographically defined proteins. For the SHA, eight amino acid sequences, 2 cycles plus one amino acid in an α helix, with strip-of-helix hydrophobicity indices greater than 2.5, were selected with overlapping segments joined. These selections were terminated according to simple 'capping rules', which took into account the roles of N-terminal Asn or Pro and C-terminal Gly in the stability of helices. In analyses of 35 crystallographically defined proteins with known α and 3₁₀ helices, the predictions with the SHA overlapped (had overlap indices χ x 0.5) with 34% of known helices, touched (had overlap indices 0.5 > x > 0) or overlapped with 66% of known helices, or were neighboring (came within 6 residues) or touched or overlapped with 82% of known helices. At each level of judging the quality of prediction, the SHA was usually less sensitive (correct predictions/total number of known helices) and more efficient (correct predictions/total number of predictions) than the Chou-Fasman and Garnier-Robson methods. It was simpler in design and calculation. The chemical mechanisms underlying these algorithms appear to apply both to protein folding and to selection of T cell-presented antigenic sequences.