AbstractAntibody–lysozyme and protease–inhibitor complexes are reconstituted by docking lysozyme as a rigid body onto the combining site of the antibodies and the inhibitors onto the active site of the proteases. Simplified protein models with one sphere per residue are subjected to simulated annealing using a crude energy function where the attractive component is proportional to the interface area. The procedure finds clusters of orientations in which a steric fit between the two protein components is achieved over a large contact surface. With five out of six complexes, the native structure of the complexes determined by X‐ray crystallography is among those retained. Docked complexes are then subjected to conformational energy refinement with full atomic detail. With Fab HyHEL 5 and lysozyme, a native‐like complex has the lowest refined energy. It can also be retrieved when starting with the X‐ray structure of free lysozyme. However, some non‐native complexes cannot be rejected: they form large interfaces, have a large number of H‐bonds, and few unpaired polar groups. While these are necessary features of protein–protein recognition, they are not sufficient in determining specificity.