Large quantities of thermodynamic parameters that characterize the formation of weakly bound complexes have dramatically accumulated in the literature. Parameters such as enthalpy and entropy changes that accompany ligand-receptor interactions contain the underlying information that richly describes the mechanism of molecular interaction and have been instrumental in revealing the mechanism of molecular recognition. Molecular recognition is ultimately achieved via intermolecular orientation; the latter has beenspecifically defined as "orientation-based fit" in the present article. In the mean field approximation, a model showed that the compensatory enthalpy-entropy relationship operates as a consequence of a complexation series being studied that occurs far enough away from the ideal complexation. Then, a dimensionless factor was proposed to measure the orientation-based fit between constituent components, in terms of the enthalpy and entropy associated with intermolecular interaction. In addition, the applicability of this dimensionless factor has been satisfactorily demonstrated in the ligand-macromolecule system that consists of small molecules and two poly(ethylene glycol) (PEG) compounds (PEG-6000 and PEG-1000). All the small-molecule-PEG systems are assigned to one of three classes, on the basis of the mechanisms of their individual weak interaction with PEG. The flexibility of PEG has conflicting effects on molecular recognition.