Solvation free energy differences

Figure 1. Thermodynamic cycle for computing solvation free energy difference between two solutes SI and S2.

M. R. Reddy and M. D. Erion, Calculation of relative solvation free energy differences... 

The solvation free energy difference between modeled and native loops is... 

M. Mezei, Mol. Simulation, 10, 225 (1993). Calculation of Solvation Free-Energy Differences for Large Solute Change from Computer Simulations with Quadrature-Based Nearly Linear Thermodynamic Integration. 

Classically, the effects of varying solvent composition are decomposed into electrostatic and hydrophobic effects. Recent reexamination of the classic Tanford experiments on contributions to change in solvation free energy differences (Auton, Holthauzen, and Bolen 2007), along with consideration of what constitutes hydro-phobicity (Chandler 2005) brings into question this taxonomy. Given the work reviewed above, we prefer to use a more natural set of variables, electrostatic and van der Waals interactions, which are conveniently part of the underlying intermolecular interaction models, to show the mechanistic trends of solution (de)stabilization. 

Figure 1 Thermodynamic cycle used to compute relative solvation free energy differences (AAG /).

M. R. Reddy and M. D. Erion, J. Comput. Chem., 20,1018 (1999), Calculation of Relative Solvation Free Energy Differences by Thermodynamic Perturbation Method Dependence of the Free Energy Results on the Simulation Length. 

This shows that the first five clustering molecules account for some 80% of the solvation free energy difference. Such a result is encouraging since it demonstrates that important insights can be obtained from supermolecule studies restricted to the inclusion of a relatively small number of solvent molecules. 

Limited testing of this parameterization led Glennon and co-workers to conclude that it was possible to reproduce experimental data regarding the structure and dynamics of carbohydrates. However, raP simulations indicated that the parameter set was unable to reproduce the experimental solvation free energy differences between a- and -Glcp (see Table 1). The poor performance of these parameters in the FEP simulations was suggested to be related to overestimation of intramolecular interaction energies in AMBER. ... 

Figure 6 The thermodynamic cycle to compute solvation free energy difference AACsoiv between two. solutes A and B in water. The vertical arrows indicate mutations carried out by free energy simulations. Solute A is mutated to B in gas phase (the left vertical arrow) and in a water box (the right vertical arrow) to obtain AGg and ACw. respectively. AAC,ioi, is calculated according to the equation below the cycle...

The zwitterion/neutral relative free energy was theoretically estimated for tyramine (25) in aqueous solution, modeling pH = 7. The experimentally found ratio is 3.7 at T = 25 "C. Using the PCM/MP2/6-31G and the FEP/MC solvation free energy differences, the zwitterionic form was strongly under- and overestimated, respectively [84]. FEP/MC simulations in the same paper pointed out... 

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