Identification of protein sequence homology by consensus template alignment.

A pattern-matching procedure is described, based on fitting templates to the sequence, which allows general structural constraints to be imposed on the patterns identified. The templates correspond to structurally conserved regions of the sequence and were initially derived from a small number of related sequences whose tertiary structures are known. The templates were then made more representative by aligning other sequences of unknown structure. Two alignments were built up containing 100 immunoglobulin variable domain sequences and 85 constant domain sequences, respectively. From each of these extended alignments, templates were generated to represent features conserved in all the sequences. These consisted mainly of patterns of hydrophobicity associated with beta-structure. For structurally conserved beta-strands with no conserved features, templates based on general secondary structure prediction principles were used to identify their possible locations. The specificity of the templates was demonstrated by their ability to identify the conserved features in known immunoglobulin and immunoglobulin-related sequences but not in other non-immunoglobulin sequences.