Applications of Thermodynamic Perturbation Formulas

3 Applications of Thermodynamic Perturbation Formulas Ligand Binding 

In these equations, the A play the role of coupling parameters. 

The same technique can be used in some cases to obtain accurate estimates of binding free energy differences for a set of ligands of interest [25, 31-34]. The molecule taken as the reference need not be a real molecule. Indeed, the reference molecule could be intermediate between a large set of molecules of interest, so that conformations that are sufficiently representative of them all are sampled in the reference simulation. The justification for this approach is discussed in detail in Chap. 6. To achieve this for a variety of substituted phenols, Liu et al. [25] added dummy atoms to the ring at the sites they wished to substitute. Such dummy atoms can be softer  

rtJ is the distance between a softened atom i on the reference molecule and another atom j etJ and are the van der Waals interaction parameters for this pair, 

As an example, consider a solution mixture of two molecules, 1 and 2. The system is described by the hybrid potential energy function  

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