Accuracy of multiple sequence alignments as assessed by reference to structural alignments

In the last 20 years, many multiple-sequence alignment programs based on various principles have been developed. Continuous e orts have been devoted to solve two major problems: (1) how to evaluate the 'goodness' of an alignment, and (2) how to get the alignment with the optimal score. These problems are tightly interrelated, and other criteria are needed to objectively assess reliability of a certain alignment method. Recently, the number of protein three-dimensional (3D) structures determined by X-ray crystallography and high-resolution NMR methods is rapidly increasing. Comparison of the 3D structures makes it possible to align distantly related protein sequences based on their structural equivalence. A few collections of such structure-based alignments are now available [4]. Hence we can assess the quality of sequence alignments obtained by a given method by referring to the structural counterparts. McClure et al. [3] recently reported that the! most popular 'progressive' metho