Electrostatic Interactions In Proteins Research Articles

Macroscopic models for studies of electrostatic interactions in proteins: limitations and applicability.

The validity of macroscopic models for calculations of electrostatic energies in proteins is examined. The Tanford-Kirkwood (TK) model is extended to include the self energy of the ionized groups. It is shown that ionized groups cannot exist inside nonpolar regions of proteins and argued that the experimental finding of ions inside proteins proves that the corresponding local environment is polar. The modified TK model (MTK model), which adjusts charge-charge interactions by the corresponding solvent accessibilities, is found to be inconsistent with the TK model, on which it is based. The MTK model corresponds to a polar interior whereas the TK model assumes a nonpolar interior. It is shown that models that assume a high dielectric constant for proteins give reasonable results for interactions between charged groups at equilibrium. It is then explained why, in contradiction to common belief, protein interiors are polar around charged groups. It is argued that in focusing on charge-charge interactions one overlooks the key contribution of the protein dipoles in determining the self energy of charges in the interior of proteins.

The pH dependence of hydrogen exchange in proteins.

The static accessibility modified discrete charge model for electrostatic interactions in proteins is extended to the prediction of the pH dependence of hydrogen exchange reactions. The exchange rate profiles of buried amide protons are shown to follow the calculated pH dependence of the electrostatic component of protein stability. Rate profiles are calculated for individual buried amide protons in ribonuclease S and bovine pancreatic trypsin inhibitor. The electrostatic free energy of stabilization of the protein and the energy required to bring the catalytic ion to an exchange site are expressed as an apparent, pH-dependent contribution to the activation energy. Changes in the electrostatic stabilization of the proteins affect the calculated exchange rate for buried amide protons by more than 1000, while local field effects raise or lower the predicted exchange rates by less than 100. The pH dependence of exchangeable protons at the protein surface, such as the C-2 imidazole protons, is shown to follow the estimated energy required to introduce the catalytic ion at the exchange site. These calculations are discussed in terms of current models for proton exchange which incorporate the dynamic nature of the structure to explain exchange data from the interior of a protein.

The reactivation of C55-isoprenoid-alcohol-phosphokinase apoprotein by lipids. Evidence for lipid hydration in lipoprotein function.

The reactivation of C55‐isoprenoid‐alcohol phosphokinase apoprotein by a variety of lipids has been investigated. A considerable lack of specificity for the chemical structure of the activating lipid is demonstrated. Reactivation appears to occur by some physical mechanism. An electrostatic interaction of protein and lipid does not appear to be important. All active lipids found are able to swell and become hydrated in aqueous buffer. Some of these lipids were active only after sonication or in the presence of detergent. The hydrated lipid phase is concluded to activate by solubilization, as a liquid‐crystalline or micellar solvent for the extremely hydrophobic enzyme apoprotein and for the non‐hydrating C55‐isoprenoid alcohol.

The Binding of Calcium to Phospholipid-Protein Complexes

SummaryThe ability of protamine, lysozyme, and bovine serum albumin to compete for calcium binding sites on acidic phospholipids provides a method for quantitative studies of the electrostatic interactions of proteins with phospholipids. The results demonstrate the reversible, stoichiometric binding of proteins with phospholipids. Crude cephalin binds arginine but not glycine, leucine, or phenylalanine. The data suggest a strong electrostatic interaction between negatively charged phospholipids and positively charged proteins and indicate that electrostatic bonding may occur in lipoproteins.