I know of no way to evaluate the statistical significance of a multiple alignment. I'm not even sure that the phrase has a mathematically definable meaning. What do you *mean* by the "significance of a multiple sequence alignment"? Once we have established that, then we can look for a way to compute (or approximate) it efficiently. ------------------------------------------------------------ Kevin Karplus karplus at soe.ucsc.edu http://www.soe.ucsc.edu/~karplus Professor of Biomolecular Engineering, University of California, Santa Cruz Undergraduate and Graduate Director, Bioinformatics (Senior member, IEEE) (Board of Directors, ISCB) Affiliations for identification only.