Determinants of protein stability and folding: Comparative analysis of beta-lactoglobulins and liver basic fatty acid binding protein

A new energy decomposition approach, aimed at identifying residues
playing a folding key role, has been applied here to three homologous
proteins, belonging to the calycin superfamily, namely bovine and
porcine beta-lactoglobulins and Liver basic fatty acid binding protein,
sharing the same beta-barrel fold and different degree of sequence
identities. All-atom, explicit solvent molecular dynamics simulations
around the native conformation were used to generate, for each of the
three proteins, energy maps which were further simplified through
eigenvalue decomposition. Analysis of the components of the eigenvector
associated with the lowest eigenvalue singled out those residues (hot
sites) behaving as strongly interacting and possible nucleation centers.
The results fit well with experimental folding data and, especially,
with the analysis of side chain-side chain interaction conservation.