An Attempt to Locate the Non-helical and Permissively Helical Sequences of Proteins: Application to the Variable Regions of Immunoglobulin Light and Heavy Chains

From a consideration of (ϕ, Ψ) values of the amino acids of myoglobin, lysozyme, the α and β chains of horse oxyhemoglobin, tosyl-α-chymotrypsin, and carboxypeptidase A, an empirical procedure of predicting whether amino-acid residues in proteins are in a non-helical or may be in a helical conformation has been developed. The conformation of an amino acid at any positionn is considered to be influenced by its nearest neighbors (the amino acids at positionsn + 1 andn - 1), and the (ϕ, Ψ) values of the middle amino acidn for the various tripeptide sequences in the known proteins are tabulated. If helical, the (ϕ, Ψ) values are plotted to define a helical (ϕ, Ψ) domain. A 20 × 20 table for all tripeptides (n - 1)-(n )-(n + 1) taken sequentially for the entire chain was constructed; it lists the number of instances in which helical and non-helical conformations for the amino acids at positionn were found. Certain sequences are found to be associated exclusively with non-helical and others exclusively with helical conformations, whereas many sequences may be either helical or non-helical. The distribution of non-helical residues serves to limit stretches of permissively helical regions; these are then further examined by the helical wheel method. As applied to cytochromec from 18 species, the only permissively helical segment found was the stretch 91-101 near the C-terminus. For the variable regions of three light and three heavy chains of immunoglobulins, upper limits of 12 and 17% α-helix, respectively, were obtained.