A method of multiple sequence alignment is described based on the double dy
namic programming (DDP) algorithm previously used for treating structural c
onstraints encountered in structure comparison and threading. Following the
se applications, the inconsistencies that emerge when trying to combine pai
r-wise alignments into a multiple alignment are reconciled by summing all t
he, possibly inconsistent, paths (low-level alignments) into a matrix which
is then used to provide a final thigh-level) alignment. This process is ap
plied to all sequence pairs and the pair-wise results combined in a simple
multiple sequence alignment program. From this alignment, further constrain
ts are selected to bias the low-level alignments in the DDP algorithm and t
he process iterated. The results, however, showed that this overall iterati
on was not needed and one-pass gave results at least as good as the 'standa
rd' progressive method of multiple sequence alignment, Further applications
of the method are discussed. (C) 2000 Elsevier Science Ltd. All rights res
erved.