A Statistical-Mechanical Model for the Binding of Flexible Ligands to Proteins

In this dissertation, a theoretical model is presented for the binding of flexible ligands to proteins. The model explicitly accounts for the ability of these chain-like molecules to bind in a large number of configurations (including many in which not all segments are in contact with the protein) and therefore is quite different from the theory of multiple equilibria which commonly is used to analyze such interactions. The latter assumes that the ligands bind rigidly to point binding sites, neglecting the internal degrees of freedom of the bound molecules. Comparisons of binding data calculated using the present model with those obtained experimentally indicate that this model, rather than the theory of multiple equilibria, is the appropriate theoretical model for the interactions between flexible ligands and proteins (e.g. the nonspecific binding of substituted alkanes to proteins)