The influence of nearest‐neighboring amino acid residues on aspects of secondary structure of proteins. Attempts to locate α‐helices and β‐sheets

The influence of nearest‐neighbor pairs of amino acids (n − 1) and (n + 1) on the conformation of amino acid (n) in proteins has been studied. From experimental data on eleven proteins of known three dimensional structures, our definition of an α‐helical domain in the Φ,Ψ plot has been reexamined and found to be satisfactory. On the same principle, a regular β‐sheet domain has been delineated. We then revised our 20 × 20 table of frequencies of occurrences of various conformations tabulating three values: α‐helical, β‐sheet, and neither. These frequencies were then used to locate the helixbreaking positions in cytochrome b₅, papain, thermolysin, and calcium‐binding protein. In conjuction with the helical wheel method, they were useful for predicting the locations of most α‐helical segments. Similarly the β‐sheet breaking positions in papain were located and most of the β‐sheets found by X‐ray diffraction were close to or between these positions. Data on β‐sheets are extremely sparse so that extensive tests were not possible. The application of this method to abnormal hemoglobins suggested possible distortions of helices and in several instances correlated with abnormal properties of the hemoglobins and association with disease. The variable region of human immunoglobin heavy chains was found to have a very low α‐helical content though β‐sheet structures might exist.