How do protein signatures compare to other ways of classifying proteins?

Multiple sequence alignments can provide us with valuable information for protein classification since they allow us to identify the (often few) amino acid residues that are conserved in distantly related proteins (Figure 11). It is not possible to identify such important residues with pairwise alignment techniques, such as BLAST. As a consequence, protein signatures built from multiple sequence alignments are usually better at detecting divergent homologues than pairwise comparison methods.

Figure 11 Multiple sequence alignment for 60S acidic ribosomal protein P0 from different organisms (eukaryota and archaea). There are two amino acids indicated by red arrows, lysine (K) and arginine (R), that are conserved in all sequences. Multiple sequence alignment methods are important for identifying highly conserved residues that are essential for stability or function of the protein.