You have asked a very complicated question, and I am not sure what you mean by a "proper ligand." One, some enzymes and some ligands change shape upon binding to each other, but not all do. Two, many forces including electrostatic ones, are responsible for binding between a ligand an an enzyme. Three, a few complexes are relatively easy to predict qualitatively, such as substrate analogs. However in among substrate analogs there are some odd cases. Perhaps a good review article on docking would be a start.