A protein is usually classified into one of the following five structu
ral classes: alpha, beta, alpha + beta, alpha/beta, and zeta (irregula
r). The structural class of a protein is correlated with its amino aci
d composition. However, given the amino acid composition of a protein,
how may one predict its structural class? Various efforts have been m
ade in addressing this problem. This review addresses the progress in
this field, with the focus on the: state of the art, which is featured
by a novel prediction algorithm and a recently developed database. Th
e novel algorithm is characterized by a covariance matrix that takes i
nto account the coupling effect among different amino acid components
of a protein. The new database was established based on the requiremen
t that the classes should have (1) as many nonhomologous structures as
possible, (2) good quality structure, and (3) typical or distinguisha
ble features for each of the structural classes concerned. The very hi
gh success rate for both the training-set proteins and the testing-set
proteins, which has been further validated by a simulated analysis an
d a jackknife analysis, indicates that it is possible to predict the s
tructural class of a protein according to its amino acid composition i
f an ideal and complete database can be established. It also suggests
that the overall fold of a protein is basically determined by its amin
o acid composition.