Mix'n'Match: an improved multiple sequence alignment procedure for distantly related proteins using secondary structure predictions, designed to be independent of the choice of gap penalty and scoring matrix

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Abstract
A new multiple sequence alignment procedure is presented. Several different multiple alignments are made using differing criteria. Having divided the sequences into strongly conserved regions (SCRs) and loosely conserved regions (LCRs), the ‘best’ alignment for each LCR is chosen, independently of the other LCRs, from a selection of possibilities in the multiple alignments. To help make this choice for each LCR, the secondary structure is predicted and shown alongside each different possible alignment. One advantage of this method over automatic, non-interactive methods, is that the final alignment is not dependent on the choice of a single set of scoring parameters. Another is that, by allowing interactive choice and by taking account of secondary structural information, the final alignment is based more on biological rather than mathematical factors. This method can produce better alignments than any of the initial automatic multiple alignment methods used.