Towards a covering set of protein family profiles

Evolutionary classification leads to an economical description of the protein sequence universe because attributes of function and structure are inherited in protein families. Efficient strategies of functional and structural genomics therefore target one representative from each family. Enumerating all families and establishing family membership consistently based on sequence similarities are nontrivial computational problems. Emerging concepts and caveats of global sequence clustering are reviewed. Explicit multiple alignments coupled with neighbourhood analysis lead to domain segmentation, and hierarchical unification helps to resolve conflicts and validate clusters. Eventually, every part of every sequence will be assigned to a domain family which is uniquely associated with a fold and a molecular function.