It is of interest to examine changes in configurational entropy, along with the component energy changes discussed above. The configurational entropy, S, may be written as an expansion in terms of first-order terms, pairwise mutual informations, third-order mutual informations, and so forth . Here, we examine only the relatively tractable first-order term S (1) , which provides a useful look at overall trends . The change in first-order entropy of ligand i on binding for dihedral angle n is obtained by binning the dihedral, φ in , into m = 1 . . . N bins to create a normalized probability distribution, and computing its first order contribution to the binding entropy as