Simultaneous comparison of three protein sequences.

Currently there are several computer algorithms available for aligning two biological sequences. When more than two sequences are to be aligned, however, pairwise comparisons using these methods rarely lead to a consistent alignment of the sequences. One obvious solution to this problem is to compare all the sequences simultaneously. Here we present an algorithm for the simultaneous comparison of three biological sequences. The algorithm is an extension of the method developed by S. B. Needleman and C. D. Wunsch, but it decreases the almost prohibitively long computing time required by a direct naive extension to a practical level: it takes time proportional to the cube of the mean sequence length, in comparison to the fifth power time taken by the direct extension. Simultaneous comparison not only gives a consistent alignment of the three sequences, but it could also reveal homologous residues in the sequences that might be overlooked by the pairwise comparisons. As an example of the application of the algorithm, three copper-containing proteins, plastocyanin, stellacyanin, and cucumber basic blue protein, are compared.