In the present study, we first revisit how cooperativity modulates the concentration of a ternary complex in equilibrium using enzyme kinetics and distinguish roles of binary protein-ligand binding affinities from cooperativity. We show that the hook effect is a direct consequence of strong binary binding, which can be alleviated by weakening the corresponding protein-ligand interaction and increasing cooperativity. To eliminate the asymmetry of cooperativity, we introduce the concept of reduced cooperativity, which captures only the non-pairwise effects of the three-body system. Under the assumption of a rigid ligand and two independent ligand-binding events in gas-phase, cooperativity can be approximated as the sum of the induced PPIs and the cooperative solvation free energy. Both quantities can be estimated from molecular dynamics (MD) simulations. Lastly, different types of induced PPIs caused by geometric perturbations are discussed, and the protein-protein geometries resolved in the crystal structures are compared.