Nucleic Acids Research, 1994, Vol. 22, No. 22 4673-4680
© 1994
COMPUTATIONAL BIOLOGY |
CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice
European Molecular Biolgoy Laboratory Postfach 102209, Meyerhofstrasse 1, D-69012 Heidelberg, Germany
*To whom correspondence should be addressed
Received July 12, 1994. Revised September 23, 1994. Accepted September 23, 1994.
The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to downweight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available.
+Present address: European Bioinformatics Institute, Hinxton Hall, Hinxton, Cambridge CB10 IRQ. UK
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