MODELS FOR STRONG-INTERACTIONS IN PROTEINS AND ENZYMES .2. INTERACTIONS OF IONS WITH THE PEPTIDE LINK AND WITH IMIDAZOLE

Cluster ions provide an experimental measure of ionic interaction energies in proteins. Peptide links, modeled by the alanine derivative CH//3CO-Ala-OCH//3, are strong hydrogen donors and bond by 30 kcal/mol to anions such as RCOO** minus and Cl** minus . The protein environment as modeled by two peptide amide groups stabilizes an anion by about 45 kcal/mol and a cation by about 50 kcal/mol. Therefore, in general, a protein backbone can stabilize a charge-separated ion pair by 90-110 kcal/mol. Applying clustering results to a specific biological system, anionic centers in the active site of serine proteases are examined. The model suggests that the aspartate carboxyl of the enzyme is solvated by four hydrogen bonds by about 65 kcal/mol, and the tetrahedral oxyanion intermediate is stabilized by hydrogen bonds to two peptide links by about 30 kcal/mol.