(4, 10pts) Chemists are capable of modifying different structural moieties on substrates in order to optimize binding to the drug target. For example, a series of substrates were designed to bind to protease to function as protease inhibitors, and their binding thermodynamic properties were determined and summarized here. Three bars under each substrate refer to their values of AG°, AH°, and (-TAS°) of binding (adapted from J. Mol. Bio. 405, 11070 (2011)).

(4B, 2pts). If the binding affinity (i.e. association equilibrium constant) increases two-fold, what is the difference on Gibbs free energy of binding?