Free energy perturbation definition

Nonetheless, this raises the question of what is an appropriate definition of the NAC. Mulholland suggests a definition that is much less arbitrary the NAC is the conformation of the substrate bound to the enzyme, and what is critical then is the free energy needed to form this conformation in aqueous solution. MulhoUand estimates this energy as 4-5 kcal mol through a free energy perturbation calculation and MD using AMI and CHARMM. This is half the estimate of Bruice and suggests that formation of the NAC is only partly responsible for the catalytic effect afforded by CM. 

Of course, the accuracy can be systematically improved by incorporating the higher order terms into the coordinate r. Anyway, with the definition tj = it is made possible to compute free energy contribution 8fi with the method completely parallel to that presented in Sect. 6.4.2. Explicitly, the distribution functions P tf) and defined, respectively, in Eqs. (6.31) and (6.32) are rewritten in terms of the perturbation energies,... 

We shall start with the so-called intermediate-field case. In many of the ionic complexes of the 3group elements, while the free ion energies due to the Coulomb repulsion between electrons have the order of magnitude of 10 to 10 cm, energies of the cubic crystal field are of the order of 10 cm. So we can treat the effect of the latter as the perturbation acting on the multiplet terms characterized by definite values of L and S. 

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