The preferential occurrence of certain disulphide-bridge topologies in prot
eins has prompted us to design a method and a program, KNOT-MATCH, for thei
r classification. The program has been applied to a database of proteins wi
th less than 65% homology and more than two disulphide bridges. We have inv
estigated whether there are topological preferences that can be used to gro
up proteins and if these can be applied to gain insight into the structural
or functional relationships among them. The classification has been perfor
med by Density Search and Hierarchical Clustering Techniques, yielding thir
teen main protein classes from the superimposition and clustering process.
It is noteworthy that besides the disulphide bridges, regular secondary str
uctures and loops frequently become correctly aligned. Although the lack of
significant sequence similarity among some clustered proteins precludes th
e easy establishment of evolutionary relationships, the program permits us
to find out important structural or functional residues upon the superimpos
ition of two protein structures apparently unrelated. The derived classific
ation can be very useful for finding relationships among proteins which wou
ld escape detection by current sequence or topology-based analytical algori
thms.