The prediction and orientation of {alpha}-helices from sequence alignments: the combined use of environment-dependent substitution tables, Fourier transform methods and helix capping rules

Amino acid substitution tables are used to estimate the extentto which amino acids in families of homologous proteins areexposed to the solvent. The approach depends on the comparisonof difference environment-dependent tables for solvent accessible/inaccessibleresidues with amino acid substitutions at each position in analigned set of sequences. The periodicity in the predicted accessible/inaccessibleresidues is calculated using a Fourier transform procedure modifiedfrom that used to calculate hydrophobic moments. a-Helices areidentified from the characteristic periodicities and the solventaccessible face of the helix is defined. The initial helix predictionsare refined using rules for identifying the N- and C-terminiof helices from sequence alignments. These rules have been definedfrom a study of protein structures. The combined method correctlypredicts 79% of the residues in helices and incorrectly predictsonly 12% of the nonhelical residues as helical. In addition,since the method is reliable at predicting the correct numberof helices in the correct position in the sequence and sinceit also predicts the internal face of each helix, the resultscan be used to postulate 3-D arrangements of the secondary structureelements.