Towards a covering set of protein family profiles

Evolutionary classification leads to an economical description of the prote in sequence universe because attributes of function and structure are inher ited 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 sequ ence similarities are nontrivial computational problems. Emerging concepts and caveats of global sequence clustering are reviewed. Explicit multiple a lignments coupled with neighbourhood analysis lead to domain segmentation, and hierarchical unification helps to resolve conflicts and validate cluste rs. Eventually, every part of every sequence will be assigned to a domain f amily which is uniquely associated with a fold and a molecular function. (C ) 2000 Elsevier Science Ltd. All rights reserved.