  Only about 1,000 qualitatively different protein folds are believed to exist
in nature. Here, we review theoretical studies which suggest that some folds
are intrinsically more designable than others, {\it i.e.} are lowest energy
states of an unusually large number of sequences. The sequences associated with
these folds are also found to be unusually thermally stable. The connection
between highly designable structures and highly stable sequences is generally
known as the "designability principle". The designability principle may help
explain the small number of natural folds, and may also guide the design of new
folds.
