We introduce a simple theoretical approach for an equilibrium study of
proteins with known native-state structures. We test our approach with
results on well-studied globular proteins, chymotrypsin inhibitor
(2ci2), barnase, and the alpha spectrin SH3 domain, and present evidence
for a hierarchical onset of order on lowering the temperature with
significant organization at the local level even at high temperatures. A
further application to the folding process of HIV-1 protease shows that
the model can be reliably used to identify key folding sites that are
responsible for the development of drug resistance.
