SPRUCE is an application that prepares biomolecular structure files (PDB, mmCIF, oeb, etc.) for downstream modeling applications, such as running a BROOD query, docking a ligand with FRED or HYBRID, predicting poses with POSIT, or for running SZMAP to analyze active-site hydration thermodynamics. The preparation workflow from an experimental or modeled structure involves, 1) expansion of the asymmetric unit to the biological unit (if structure is from an X-ray crystallography experiment and it it is necessary), 2) enumeration (default) or collapse of alternate locations, 3) building missing pieces e.g. partial sidechains and capping chain breaks, 4) placement and optimization of hydrogen atoms including tautomer enumeration of ligands and cofactors, as well as evaluation of those tautomer states in the biomolecule structure.