STRUCLA: a WWW meta-server for protein structure comparison and evolutionary classification.

Evolutionary relationships of proteins have long been derived from the alignment of protein sequences. But from the view of function, most restraints of evolutionary divergence operate at the level of tertiary structure. It has been demonstrated that quantitative measures of dissimilarity in families of structurally similar proteins can be applied to the construction of trees from a comparison of their three-dimensional structures. However, no convenient tool is publicly available to carry out such analyses. We developed STRUCLA (STRUcture CLAssification), a WWW tool for generation of trees based on evolutionary distances inferred from protein structures according to various methods. The server takes as an input a list of PDB files or the initial alignment of protein coordinates provided by the user (for instance exported from SWISS PDB VIEWER). The user specifies the distance cutoff and selects the distance measures. The server returns series of unrooted trees in the NEXUS format and corresponding distance matrices, as well as a consensus tree. The results can be used as an alternative and a complement to a fixed hierarchy of current protein structure databases. It can complement sequence-based phylogenetic analysis in the 'twilight zone of homology', where amino acid sequences are too diverged to provide reliable relationships.