Fold assignments for newly sequenced genomes belong to the most important a
nd interesting applications of the booming field of protein structure predi
ction. We present a brief survey and a discussion of such assignments compl
eted to date, using as an example several fold assignment projects for prot
eins from the Escherichia coli genome. This review focuses on steps that ar
e necessary to go beyond the simple assignment projects and into the develo
pment of tools extending our understanding of functions of proteins in newl
y sequenced genomes. This paper also discusses several problems seldom addr
essed in the literature, such as the problem of domain prediction and compl
ementary predictions (e.g., transmembrane regions and flexible regions) and
cross-correlation of predictions from different servers. The influence of
sequence and structure database growth on prediction success is also addres
sed. Finally, we discuss the perspectives of the field in the context of ma
ssive sequence and structure determination projects, as well as the develop
ment of novel prediction methods. (C) 2001 Academic Press.