Though DOCK is typically used to process small molecules, it can be used to study the interactions of macromolecular ligands. The chief difference in protocol is that to use the match_receptor_sites procedure for the orientation search, then special ligand centers must be used to represent the ligand. This is signaled by setting the ligand_centers parameter. The ligand centers may be constructed by sphgen and must reside in a file identified with the ligand_center_file parameter. See Shoichet, et al. J. Mol. Biol. 1991 for examples and discussion of macromolecular docking.