Identifying residues that interact with ligands is useful as a first step to understanding protein function and as an aid to designing small molecules that target the protein for interaction. Several studies have shown that sequence features are very informative for this type of prediction, while structure features have also been useful when structure is available. We develop a sequence-based method, called LIBRUS, that combines homology-based transfer and direct prediction using machine learning and compare it to previous sequence-based work and current structure-based methods.