Possible models to explain the binding of a ligand, covalently attached to the surface of a protein by the “linker”, to the active site of that protein. When the ligand is bound at the active site, the linker: (A) has low conformational mobility (i.e., free rotations of the bonds of the linker are significantly restricted), (B) has significant conformational mobility, or (C) and (D) makes stabilizing contacts with the surface of the protein. In (D), the linker makes contacts with the surface of the protein even when the ligand is not bound at the active site.