Absolute free energy of solvation

In Eqs. (25) and (26), the summations are over the incremental steps in going from X to Y in the gas phase or in solution. The Hj are the intermediate Hamiltonians (or force fields in a classical treatment). Thus, Hi=0,gas = Hx,gas, Hi=Njgas = HY,gas, etc. It is of course desirable that the molecules X and Y be structurally similar, so that the perturbation of X that produces Y be small. Another option is to let Y be composed of noninteracting dummy) atoms,75 so that its free energy of solvation is zero. Then Eq. (24) gives the absolute free energy of solvation of X ... 

Table 11.3 Absolute free energies of solvation (kcal mol ) and chloroform/water partition coefficients (logio units) for nucleic acid bases at the SM5.4/AM1 Icvcf ...

The SMx aqueous solvation models, of which the most successful are called AM1-SM2,27 AMl-SMla, and PM3-SM3, °- adopt this quantum statistical approach, which takes account of the ENP and CDS terms on a consistent footing. The NDDO models employed are specified as the first element (AMI or PM3) of each identifier. It is worth emphasizing that the SMx models specifically calculate the absolute free energy of solvation—a quantity not easily obtained with other approaches. We have reviewed the development and performance of the models elsewhere.203 We anticipate our further observations later in this chapter by noting that the mean unsigned error in predicted free energies of solvation is about 0.6-0.9 kcal/mol for the SMx models for a data set of 150 neutral solutes that spans a wide variety of functionalities. A number of examples are provided later in this chapter. 

J. Gao,/. Phys. Chem., 96, 537 (1992). Absolute Free Energy of Solvation from Monte Carlo... 

Poisson-Boltzmann model The PB approximation is one of the more elaborate continuum solvation models that take into account not only the charge density of the solute but also the mobile charge density within the surrounding continuum. Continuum models of solvation are in general capable of calculating absolute free energies of solvation. 

In this procedure, the electronic terms of the QM/MM interaction Hamiltonian for A and B are first annihilated, leaving only the Lennard-Jones terms, which are gradually mutated from structure A into structure B. The latter mutation consists of empirical potentials, while standard methods are employed for the conversion.Absolute free energies of solvation can also be determined following a procedure developed by Cieplak and Koll-man, in which A is made to vanish in solution ... 

Statistical Mechanical methods These methods can be used in the context of MD and MC simulations to estimate differences in free energy of solvation between reactants and products, or even to obtain the absolute free energy of solvation of molecules (for review see references 14-17). Statistical Mechanical methods are based in... 

It is worth noting that when A and B are reactants and products, equations 9 and 10 yield directly the difference in free energy of solvation, since AG = AAGsolv- On the contrary, if B is defined as a dummy molecule, then the absolute free energy of solvation is determined (AG = -AGsoiv(A)). 

The last term in equation 17, which is required for accurate calculations of the absolute free energies of solvation, is modified differently for various SMx models. For example, in SM2 and SM3 versions it has the following form... 

---