Despite progress in modeling host-guest binding interactions, these systems remain a challenging test case for binding free energy calculations, and capture some of the same challenges as protein-ligand binding free energy calculations. Thus they are likely to remain a helpful test case for the field for some time to come. host_guest. An archive copy of SAMPL9 GitHub repository hostguest challenge directory is also available in the Supplementary Documents bundle (SAMPL9-supplementary-documents.tar.gz).