PALI - a database of Phylogeny and ALIgnment of homologous protein structures

PALI (release 1.2) contains three-dimensional (3-D) structure-dependent seq uence alignments as well as structure-based phylogenetic trees of homologou s protein domains in various families. The data set of homologous protein s tructures has been derived by consulting the SCOP database (release 1.50) a nd the data set comprises 604 families of homologous proteins involving 273 9 protein domain structures with each family made up of at least two member s. Each member in a family has been structurally aligned with every other m ember in the same family (pairwise alignment) and all the members in the fa mily are also aligned using simultaneous superposition (multiple alignment) . The structural alignments are performed largely automatically, with manua l interventions especially in the cases of distantly related proteins, usin g the program STAMP (version 4.2). Every family is also associated with two dendrograms, calculated using PHYLIP (version 3.5), one based on a structu ral dissimilarity metric defined for every pairwise alignment and the other based on similarity of topologically equivalent residues. These dendrogram s enable easy comparison of sequence and structure-based relationships amon g the members in a family. Structure-based alignments with the details of s tructural and sequence similarities, superposed coordinate sets and dendrog rams can be accessed conveniently using a web interface. The database can b e queried for protein pairs with sequence or structural similarities fallin g within a specified range. Thus PALI forms a useful resource to help in an alysing the relationship between sequence and structure variation at a give n level of sequence similarity. PALI also contains over 653 'orphans' (sing le member families). Using the web interface involving PSI BLAST and PHYLIP it is possible to associate the sequence of a new protein with one of the families in PALI and generate a phylogenetic tree combining the query seque nce and proteins of known 3-D structure. The database with the web interfac ed search and dendrogram generation tools can be accessed at http://pauling .mbu.iisc.ernet.in/similar to pali.