Perturbation theory free-energy differences

Perturbation theory is also used to calculate free energy differences between distinct systems by computer simulation. This computational alchemy is accomplished by the use of a switching parameter X, ranging from zero to one, that transfonns tire Hamiltonian of one system to the other. The linear relation... 

Free energy perturbation (FEP) theory is now widely used as a tool in computational chemistry and biochemistry [91]. It has been applied to detennine differences in the free energies of solvation of two solutes, free energy differences in confonnational or tautomeric fonns of the same solute by mutating one molecule or fonn into the other. Figure A2.3.20 illustrates this for the mutation of CFt OFl CFt CFt [92]. 

Calculating Free Energy Differences Using Perturbation Theory... 

Thermodynamic perturbation theory represents a powerful tool for evaluating free energy differences in complex molecular assemblies. Like any method, however, FEP has limitations of its own, and particular care should be taken not only when carrying out this type of statistical simulations, but also when interpreting their results. We summarize in a number of guidelines the important concepts and features of FEP calculations developed in this chapter ... 

In the canonical partition function of (5.1), we have for simplicity ignored combinatorial prefactors. Free energy perturbation theory [12] relies on evaluating effectively the ratio of the partition functions to obtain the free energy difference between the initial and final states corresponding to coupling parameters A = 1 and 0 (see also Chap. 2),... 

The values AF0 m and AFi m have been calculated by using standard Statistical Perturbation Theory. Thus, equation (45) expresses the free energy difference between systems with mapping potentials Hj and Hj by... 

Chipot, C., Pohorille, A. Calculating Free Energy Differences Using Perturbation Theory, Springer Series in Chemical Physics (Free Energy Calculations), Vol. 86, Springer, Berlin, 2007, pp. 33-75. 

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