Continuum electrostatics of proteins: Experimental test with model solvents and the method of the proteins pK calculations

The experimental study of the ion's transfer energies in several model solvents has shown that for ions mimicking the large prosthetic groups the continuum electrostatics works well; for a small ion, e.g., acetate, the experimental and the calculated values differ by order of magnitude. This is because the continuum electrostatics does not account explicitly the short-range interactions, especially hydrogen bonds. To circumvent this difficulty, the method of pK calculation has been proposed that combines the experimental pKs in dimethylformamide and electrostatics calculations for the acid transfer from DMF into protein. The pre-existing intraglobular electric field is calculated using the optical dielectric constant while for the energy of dielectric response the static one is employed. For α-chymotrypsin, the calculated pKs of His57 (active site) and of His40 (surface) agree with experiment only with account of an increase in the static dielectric permittivity in the globule's outer part. Employing the same dielectric permittivity for the pre-existing field and for the dielectric response leads to an unrealistically high effective dielectric constant.