A method for multiple sequence alignment with gaps

J Mol Biol. 1989 Oct 20;209(4):539-48. doi: 10.1016/0022-2836(89)90592-5.


A method that performs multiple sequence alignment by cyclical use of the standard pairwise Needleman-Wunsch algorithm is presented. The required central processor unit time is of the same order of magnitude as the standard Needleman-Wunsch pairwise implementation. Comparison with the one known case where the optimal multiple sequence alignment has been rigorously determined shows that in practice the proposed method finds the mathematically optimal solution. The more interesting question of the biological usefulness of such multiple sequence alignment over pairwise approaches is assessed using protein families whose X-ray structures are known. The two such cases studied, the subdomains of the ricin B-chain and the S-domains of virus coat proteins, have low pairwise similarity and thus fail to align correctly under standard pairwise sequence comparison. In both cases the multiple sequence alignment produced by the proposed technique, apart from minor deviations at loop regions, correctly predicts the true structural alignment. Thus, given many sequences of low pairwise similarity, the proposed multiple sequence method, can extract any familial similarity and so produce a sequence alignment consistent with the underlying structural homology.

MeSH terms

  • Algorithms*
  • Base Composition
  • Base Sequence*
  • Molecular Probe Techniques*
  • Oligonucleotide Probes


  • Oligonucleotide Probes