Biomedical subjects

W S Sandberg

Publications and source records attributed to W S Sandberg.

3 recordsLinked to original sources

PubMed1991

Energetics of repacking a protein interior.

To test whether interactions in the hydrophobic core of a protein can be adequately modeled based on the properties of a liquid hydrocarbon, we measured the unfolding free energies of the wild-type bacteriophage f1 gene V protein and 29 mutants with apolar substitutions at positions 35 and 47. Stability changes arising from identical mutations at these two buried sites are quite different, suggesting that one site is more rigid than the other. Reversals of residues at positions 35 and 47 confirm that their environments are distinct. Mutants containing weakly polar residues at these two sites suggest that the protein interior is more polar than a liquid hydrocarbon. Interactions between residues at the two sites appear to be minimal. These observations are compatible with a view of protein interiors that incorporates properties of liquid hydrocarbons but also includes polar interactions and a site-dependent "packing energy" associated with changes in internal structure.

Calorimetry↗

PubMed1991

Repacking protein interiors.

Several goals of protein engineering may be achieved through redesign and repacking of protein interiors. The effects of interior apolar substitutions on protein stability depend strongly on the site of the substitution. One reason for this is that protein interiors have properties both of apolar liquids and of crystalline solids. Substitutions at interior sites affect the stability of a protein by changing the hydrophobicity, but each site in a protein has a characteristic energy associated with introducing packing changes, and the net stability depends on both of these factors.

Models, Chemical↗

PubMed1989

Influence of interior packing and hydrophobicity on the stability of a protein.

Protein interiors contain many tightly packed apolar atoms in a nearly crystalline state. Both shielding of apolar atoms from solvent and efficient interior packing arrangements affect protein stability, but their relative importance is unclear. To separate these effects, the stabilities of wild-type and mutant gene V proteins from bacteriophage fl were studied by measuring resistance to denaturation. The effects of subtle interior packing changes, both separate from and combined with changes in buried side chain hydrophobicity, were measured. For the interior apolar-to-apolar substitutions studied, the two effects were of the same magnitude and alteration of packing without accompanying hydrophobicity changes substantially destabilized the protein.

Calorimetry↗