Structural data of biomolecules, such as those of proteins and nucleic acids, provide much information for estimation of their functions. For structure-unknown proteins, structure information is obtainable by modeling their structures based on sequence similarity of proteins. Moreover, information related to ligands or ligand-binding sites is necessary to elucidate protein functions because the binding of ligands can engender not only the activation and inactivation of the proteins but also the modification of protein functions. This chapter presents methods using our profile-profile alignment server FORTE and the PoSSuM ligand-binding site database for prediction of the structure and potential ligand-binding sites of structure-unknown and function-unknown proteins, aimed at protein function prediction.