Free energy calculations linear response method

X Chen, A Tropsha. A generalized linear response method Application to the hydration free energy calculations. J Comput Chem 20 749-759, 1999. 

The diabatic free energy profile obtained by the method is plotted in Figures 2.11. The most notable feature of the figures is that it is essentially parabolic with respect to the reaction coordinate. This is nothing but the manifestation of the central limiting theorem, and the results indicate that the response of solvent fluctuation to the electrostatic filed is linear. The behavior, however, is not trivial, because the free energy calculated via Eqs. (2.61) and (2.62) are inherently non-linear. 

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