An algorithm for identifying similar amino acid clusters among different alpha-helical coiled-coil proteins using their secondary structure

We describe a simple approach for finding identical amino acid clusters on the outer surface of alpha -helical coiled-coil proteins by examining the s equence of amino acids that compose the protein. Finding such similarities is an important immunological problem, since these may correspond to cross- reactive epitopes, i.e., sites at which antibodies produced against one pro tein also bind to another conformationally similar protein. Because of the regularities inherent in a coiled-coil structure the position of each amino acid on the structure is predicted. Based on this prediction, our algorith m finds similarities on the outer surface of the proteins. The matches foun d by our algorithm serve as an important screening process, intended to ind icate which experiments to conduct to determine sites that correspond to cr oss-reactive epitopes. The location of several cross-reactive epitopes betw een M proteins and myosins had been verified experimentally. Although our a pproach makes many simplifying assumptions, these epitopes always correspon d to clusters of identical amino acids, which out algorithm predicted to be contiguous on the outer surface. Our algorithm runs in O (n + m + r) time and O (n + m) space, where n and m are the lengths of the protein sequences , and r is the number of matching amino acids that appear in the same struc tural position of the alpha -helix in both sequences.