Here, we investigate the potential of Dynamic Undocking (DUck) as a method to predict ΔΔGbind. DUck was introduced as a post-docking filter in virtual screening campaigns, showing an 80% to 95% reduction of docking false positives. It is a particular implementation of Steered Molecular Dynamics (SMD) used to very efficiently evaluate the mechanical stability of protein-ligand hydrogen bonds. The computed magnitude is the free energy of breaking native contacts, reaching a socalled Quasi-Bound state (ΔGQB). The predictive power of DUck was unexpected because ΔGQB is a local property with no correspondence to any macroscopic observable (Figure ). As such, it cannot predict absolute binding free energies. However, previously we have shown that: 1) most protein-ligand complexes present high ΔGQB values (i.e. they form mechanically robust hydrogen bonds); 2) correct binding modes are generally also the ones with highest ΔGQB values and, most surprisingly, 3) ΔGQB quantitatively predicted ΔΔGbind of the ternary complex between Cereblon, Lenalidomide, and various mutant forms of Casein Kinase 1⍺. This prompted us to investigate whether ΔGQB can rank-order congeneric series of protein-ligand complexes and, if so, why this magnitude would provide any insight into thermodynamic properties.