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.
Ragona
Laura
L
Laboratorio NMR, ISMAC, CNR, Milano, Italy.
Colombo
Giorgio
G
Catalano
Maddalena
M
Molinari
Henriette
H
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002417:Cattle; D003198:Computer Simulation; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007782:Lactoglobulins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D013552:Swine
D000596:Amino Acids; D050556:Fatty Acid-Binding Proteins; D007782:Lactoglobulins