Electrostatic solvation free

Hummer, G. Pratt, L. Garcia, A. E., Multistate Gaussian model for electrostatic solvation free energies, J. Am. Chem. Soc. 1997,119, 8523-8527... 

It is clear in both of these studies that the small cavity size (which fails to entirely contain all of the atoms given standard van der Waals radii) causes electrostatic solvation free energies to be seriously overestimated — the difference in the 4-nitroimidazole system seems much too large to be physically reasonable. This overestimation would be still more severe were a correct DO model to have been used (i.e., one which accounted self-consistently for the full solute polarization using eq 30). Nevertheless, the D02 results may be considered qualitatively useful, to the extent that they identify trends in tautomer electrostatic solvation free energies. 

Quantum-Mechanical Electrostatic Solvation Free Energy... 

In the semiempirical QM solvation model described here the electrostatic contribution to the solvation free energy was obtained using MD simulations [115,116]. The FEP or TI methods were used to compute the electrostatic solvation free energy as described in Sec. 3.2.2. The coupling parameter, A, for scaling the QM/ MM electrostatic terms in the MD simulations was introduced as follows ... 

A computationally attractive alternative to a direct solution of Eq. (1) is the popular Generalized Bom (GB) formalism [5,27] given in Eq. (2) which empirically approximates electrostatic solvation free energies from Poisson theory ... 

The non-polar component of the solvation free energy is especially important for implicit membrane models as it decreases from a significant positive contribution in aqueous solvent to near zero at the center of the phospholipid bilayer. Without a non-polar term, even hydrophobic solutes would in fact prefer the high-dielectric environment where the electrostatic solvation free energy is more favorable than in a low-dielectric medium. The functional form of the non-polar term may follow a simple switching function [79,80], a calculated free energy insertion profile for molecular oxygen [82,84], or may be parameterized as well with respect to simulation or experimental data. 

The first three terms in Eq. (2) are calculated using the Cornell force field [8] with no cutoff. The electrostatic solvation free energy is calculated by solving the Poisson-Boltzmann equation with the Delphi software [9, 10], which has been shown to constitute a good compromise between accuracy and computing time. 

The reaction field of the solvent is obtained as a set of polarization charges placed on the solute van der Waals surface and the electrostatic solvation free energy is calculated as... 

At the most complex level we use equation (24) to present the results in the form of Table 5. Table 5 shows the inhibitor-enzyme (column 2) and enzyme components (column 3) of the relative binding free energy. These are then divided into sub components. The sub components are the molecular mechanics terms (E, row 1 beneath inhibitor), solute entropy terms (-TS, ,, row 2 beneath inhibitor), electrostatic solvation free energy terms (AG, row 3 beneath inhibitor), nonpolar solvation terms (AG , row 4 beneath inhibitor), and the total solution phase free energy (G, row 5 beneath inhibitor). Column 4 of the table gives the total values for all sub components, these are obtained by summing columns 2 and 3 for a particular subcomponent. 

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