Understanding the determinants of stability and folding of small globular proteins from their energetics

The results of minimal model calculations indicate that the stability
and the kinetic accessibility of the native state of small globular
proteins are controlled by few ``hot'' sites. By means of molecular
dynamics simulations around the native conformation, which describe the
protein and the surrounding solvent at the all-atom level, an accurate
and compact energetic map of the native state of the protein is
generated. This map is further simplified by means of an eigenvalue
decomposition. The components of the eigenvector associated with the
lowest eigenvalue indicate which hot sites are likely to be responsible
for the stability and for the rapid folding of the protein. The
comparison of the results of the model with the findings of mutagenesis
experiments performed for four small proteins show that the eigenvalue
decomposition method is able to identify between 60\% and 80\% of these
(hot) sites.