Free energy coupling

C. Jarque and B. Tidor, Simulated annealing on coupled free energy surfaces Relative... 

The PMF as a function of Xs is determined by a coupled free energy perturbation and umbrella sampling technique.5,14,16,41 The computational procedure follows two steps, although they are performed in the same simulation. The first is to use a reference potential rp to enforce the orientation polarization of the solvent system along the reaction path. A convenient choice of the reference potential, which is called mapping potential in Warshel s work,13,14,16,42 is a linear combination of the reactant and product diabatic potential energy ... 

The average of Fa over the angles yields Fa = tiLDW - TiLDAJVSj p / 3, and the average coupling free-energy density term is expressed as... 

U. C. Singh, Proc. Natl. Acad. Sci. U.S.A., 85, 4280 (1988). Probing the Salt Bridge in the Dihydrofolate Reductase Methotrexate Complex by Using the Coordinate Coupled Free Energy Perturbation Method. 

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