It is emerging that not only protein structure, but also protein dynamics and conformational equilibria in proteins control to an important extent protein function. This holds for enzymes, where often conformational transitions determine the overall rate, but also for protein-ligand or protein-protein recognition. When nature makes use of the conformational equilibria to implement certain functionality in proteins, the question naturally arises whether redesigning those conformational equilibria would also enable us to manipulate protein properties. In this work, we demonstrate this for protein-protein binding using ubiquitin as a test case. Ubiquitin is a protein with promiscuous binding activity, which is controlled by ubiquitin's global conformational dynamics. These global conformational dynamics are dominated by a collective motion between an open and a closed state. In most complexes, ubiquitin binds preferentially in either the open or the closed state. In native unbound ubiquitin the ratio between the open and closed state is approximately one, suggesting that shifting the equilibrium to either the open or the closed state, would reduce binding to the non-compatible binding partners. Using a molecular dynamics based protein design protocol, we screened 126 core mutants of ubiquitin and identified several that shift the conformational equilibrium between the open and closed state. The change in binding free energy of those mutants to several complexes was verified, both computationally and experimentally (using NMR titration). The observed affinity patterns quantitatively agree with the predictions, thereby showing that, indeed, a shift in the conformational equilibrium enables us to shift ubiquitin's binding specificity and hence its function. Thus, exploiting the fact that conformational selection depends on the concentration of binding-competent states, a novel route towards designing specific binding by conformational shift was demonstrated.