We present an analysis of the assumptions behind
some of the most commonly used methods for evaluating the
goodness of the fit between a sequence and a structure.
Our studies on a lattice model show that methods based
on statistical considerations are easy to use and can capture
some of the features of protein-like sequences and their
corresponding native states, but unfortunately are incapable
of recognizing, with certainty, the native-like conformation
of a sequence among a set of decoys. Meanwhile, an optimization
method, entailing the determination of the parameters of
an effective free energy of interaction, is much more reliable
in recognizing the native state of a sequence. However,
the statistical method is shown to perform quite well in
tests of protein design.