The GDCC TEETOA host has some degree of conformational flexibility which can be modulated by binding and by the guest orientation and identity. Thus, we performed additional calculations in which we applied the BLUES approach to better understand the preferred orientations of the host's four ethyl groups near the cavity opening. BLUES uses a hybrid of nonequilibrium candidate Monte Carlo (NCMC) and MD moves to enhance sampling of ligand binding modes for fragment-like small molecules in binding sites , rearrangements of receptor sidechains on ligand binding , rotation of internal torsions in ligands , and rearrangement of buried water molecules on ligand binding . More details of the approach can be found in prior work . The BLUES package is freely available on GitHub at . Here, we used BLUES moves to enhance sampling of the host ethyl groups in particular.