Open-ComBind provides a pipeline (Figure ) that prepares protein and ligand structures for docking, a suite of methods to compute the similarity of features from pairs of docked ligands, as well as predicting a set of poses utilizing pre-computed similarity distributions. Protein-ligand ground-truth complexes, usually determined via X-ray crystallography, are manipulated to extract separate protein and ligand structures after alignment of the pocket residues of similar protein structures. Ligands are prepared for docking by generating a set of low-energy 3D ligand conformations. Docking is run on a single receptor conformation with all of the generated conformers per ligand and the output for each ligand is sorted according to its docking score. The user provides a docking ligand, a holo receptor structure, and a defined binding pocket on the structure. The user can then define a set of helper ligands: molecules with < 1µM affinity to the receptor but not requiring any bound structure.