1. A computer-based method for modeling 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; 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 the target macromolecule; d) mapping spatial relationships between the substructure atoms of the query ligand and the comparison ligand such that corresponding atoms are identified; e) assigning atomic coordinates to the corresponding atoms of the query ligand; f) generating 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).