As a consequence, tests of computational methods often make use of low molecular weight receptor molecules, called hosts, in place of proteins - . A typical host, beta-cyclodextrin (β-CD; Figure ), is more than an order of magnitude less massive than even a small globular protein comprising ~100 residues, and many proteins of pharmaceutical interest are 5-10 times larger. Furthermore, hosts tend to be comparatively rigid, because they are usually both macrocyclic and polycyclic and therefore have few freely rotatable bonds per unit mass. Nonetheless, the same basic forces and physical chemistry are at work in host-guest binding as in protein-small molecule binding. For example, both proteins and hosts can form hydrogen bonds and hydrophobic interactions with the molecules they bind, and the same statistical thermodynamics framework applies to them . The cyclodextrins represent the least expensive and most abundant class of host molecules, as they can be synthesized from starch using readily available enzymes . The most common cyclodextrins, α-cyclodextrin, βcyclodextrin (β-CD), and γ-cyclodextrin, are macrocycles of 5, 6 or 7 glucose units respectively (Figure ). They possess a hydrophobic cavity which is open at two ends. The rim of the larger opening is called the secondary face because of its 14 secondary hydroxyl groups, and the rim of the smaller opening is called the primary face because of its 7 primary hydroxyl groups. The polar hydroxyl groups contribute to the water solubility of these nonionic molecules, and aqueous binding affinities have been measured for native cyclodextrins with a variety of guest molecules - . These data are useful for testing computational models of binding but are sharply limited in the types of noncovalent interactions they probe, because although one may vary the guest compounds used, the host is uniformly a simple glucose polymer. Greater diversity in binding interactions may be accessed by using derivatives of the cyclodextrins. Binding data have also been generated for some cyclodextrin derivatives - , but the range of noncovalent interactions these probe falls short of that routinely explored by medicinal chemists. Other families of hosts, such as those based on the glycouril unit , the deep cavity cavitands , and molecular clips and tweezers , , offer valuable additional diversity but still fail to explore a full variety of drug-related interactions.