If the ATP-binding site of an enzyme is buried in the interior of the enzyme, in a hydrophobic environment, is the ionic interaction between enzyme and substrate stronger or weaker than that same interaction would be on the surface of the enzyme, exposed to water? Why?

Stronger; a hydrophobic has lower dielectric constant. The lower the dielectric constant of the interior, the stronger the ionic interactions.

Explanation:

Ionic interactions are the electrostatic interactions between the oppositely charged ions. The strength of ionic interaction depends on the magnitude of the charges on the ions, the distance between the charged groups and the dielectric constant.

Here, the dielectric constant is the property of the medium in which the ionic interactions are taking place. Dielectric constant represents the number of dipoles present in the medium or solvent. A medium with higher dielectric constant would attract the oppositely charged ions towards its own dipole and would thereby, make the ionic interaction between the ions weaker.

Given that the ionic bonding between substrate and enzyme is taking place in the hydrophobic interior, ionic interactions would be stronger since the hydrophobic medium has a lower dielectric constant.

The lower number of the electric dipoles or their absence in the hydrophobic interior would not attract the oppositely charged groups of substrate and enzyme towards its own dipoles as the water with higher dielectric constant would have done. This would allow stronger ionic interaction between the substrate and the enzyme.