Abstract: Embodiments herein describe systems and methods to predict biomolecule-ligand complexes and uses thereof. Many embodiments generate candidate poses and docking scores for ligands known to interact with a target protein as well as a candidate ligand. Based on similarities present in the candidate poses and docking scores, a pose for the candidate ligand is identified. Many embodiments determine whether a candidate ligand can bind to a target and, if so, determine an affinity. Many embodiments can be used for virtual screening or lead optimization.