Abstract

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 down-weight 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.

Keywords

BiologySequence (biology)Position (finance)WeightingMultiple sequence alignmentSensitivity (control systems)Sequence alignmentMatrix (chemical analysis)GeneticsComputational biologyPeptide sequenceGene

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Publication Info

Year
1994
Type
article
Volume
22
Issue
22
Pages
4673-4680
Citations
64103
Access
Closed

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Julie Thompson, Desmond G. Higgins, Toby J. Gibson (1994). CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research , 22 (22) , 4673-4680. https://doi.org/10.1093/nar/22.22.4673

Identifiers

DOI
10.1093/nar/22.22.4673