Protein folds and families: sequence and structure alignments

Dali and HSSP are derived databases organizing protein space in the structu rally known regions. We use an automatic structure alignment program (Dali) for the classification of all known 3D structures based on all-against-all comparison of 3D structures in the Protein Data Bank. The HSSP database as sociates 1D sequences with known 3D structures using a position-weighted dy namic programming method for sequence profile alignment (MaxHom). As a resu lt, the HSSP database not only provides aligned sequence families, but also implies secondary and tertiary structures covering 36% of all sequences in Swiss-Prot. The structure classification by Dali and the sequence families in HSSP can be browsed jointly from a web interface providing a rich netwo rk of links between neighbours in fold space, between domains and proteins, and between structures and sequences. In particular this results in a data base of explicit multiple alignments of protein families in the twilight zo ne of sequence similarity. The organization of protein structures and famil ies provides a map of the currently known regions of the protein universe t hat is useful for the analysis of folding principles, for the evolutionary unification of protein families and for maximizing the information return f rom experimental structure determination. The databases are available from http://www.embl-ebi.ac.uk/dali/.