Relative binding free energy (ΔΔGbind) calculations provide a useful shortcut when investigating a congeneric series of compounds that explore a similar configurational space. Path-sampling methods aim to explore this (presumably) complex landscape to predict the kinetic and thermodynamic observables. DUck introduces only a small perturbation to the bound state, yielding the free energy of the process. Contrary to expectation, this local property can, under certain conditions, inform about macroscopic observables.