It is important to note the difference between the binding free energy (∆G A-B ), the binding free energy in the stabilized state (∆G s A-B ), and induced PPIs (∆G induced A-B ). Figure shows an example of a weakly interacting protein pair with an energetically unfavorable stabilized binary state but with strong induced PPIs, i.e., ∆G induced A-B << ∆G A-B < 0 < ∆G s A-B . In this example, the stabilized binary state AB s is difficult to reach from the individual protein states A and B because of the net positive free-energy difference due to the high unary perturbation ∆G s geo,A and ∆G s geo,B . In contrast, the induced PPIs only consider the binding between the already perturbed (stabilized) proteins to form the stabilized binary state.