1. A computer-based method for generating 3-D structural models of complex formation between a query ligand and a target macromolecule, the method comprising: a) providing a structural model of a query ligand and a structural model of a target macromolecule; wherein the structural model of the query ligand is based on data from X-ray crystallography or NMR spectroscopy, and the structural model of the target macromolecule is based on data from X-ray crystallography; b) identifying a substructure of the query ligand; c) identifying comparison ligands in a set of 3-D structural models that each share an identical substructure with the query ligand, wherein each 3-D structural model comprises a comparison ligand and a comparison macromolecule, and wherein the comparison macromolecule has structural features homologous to structural features of the target macromolecule of 20% or greater nucleic acid and/or amino acid homology; d) mapping spatial relationships between the substructure atoms of the query ligand and a comparison ligand identified in c) such that corresponding atoms are identified; e) assigning atomic coordinates to the corresponding atoms of the query ligand; f) generating and displaying one or more output models, each model comprising a 3-D structural model of the query ligand substructure and the target macromolecule, wherein the 3-D model of the query ligand substructure comprises the atomic coordinates of the query ligand from step (e).