Solvent-accessible surface area term

AGg (X) can be removed by assuming that it is equivalent to the polar contribution to the free energy of solution of solute X in a nonpolar hydrocarbon solvent, such as squalane. A second reason for using a reference hydrocarbon solvent is to correct, at least partially, for the fact that the hardcore van der Haals volume is a poor estimate of the size of the cavity and its accessible surface for solvent interactions for aromatic and cyclic solutes. The solvent accessible surface area would logically be the preferred parameter for the cavity term but is very difficult to calculate while the van der Haals volume is readily accessible. With the above approximations the solvent interaction term for... 

Non-electrostatic terms, comprising the solvent-solvent cavity term and solute-solvent van der Waals term, may be linearly related to solvent-accessible surface area (SA)... 

Our extension of the LIE approach to calculate free energies of hydration (AGhyd) incorporated a third term proportional to the solute s solvent-accessible surface area (SASA), as an index for cavity formation within the solvent.19,27 The latter term is needed for cases with positive AGhyd such as alkanes and additional improvement occurred when both a and P were allowed to vary. Equation 8 gives the corresponding LIE/SA equation for... 

Part of the motivation behind so straightforward an approach derives from its ready application to certain simple systems, such as the solvation of alkanes in water. Figure 11.8 illustrates the remarkably good linear relationship between alkane solvation free energies and their exposed surface area. Insofar as the alkane data reflect cavitation, dispersion, and the hydrophobic effect, this seems to provide some support for the notion that these various terms, or at least their sum, can indeed be assumed to contribute in a manner proportional to solvent-accessible surface area (SASA). 

Among further CPSA descriptors are the differences between PPSA and PNSA, and fractional values as ratios of PPSA or PNSA and the total molecular surface area. For the original list of 25 CPSA descriptors as well as for recent extensions, the reader is referred to the literature (Stanton and Jurs, 1990 Aptula et al., 2003 Mattioni et al., 2003 Mosier et al., 2003). It should be further noted that, in contrast to the initially introduced electrostatic molecular surface interaction terms (Grigoras, 1990), the CPSA descriptors were actually defined using solvent accessible surface areas instead of simple van der Waals surface areas (Stanton and Jurs, 1990), a fact that is ignored in the present discussion for the sake of simplicity. 

The area of the solvent-accessible surface is called the Solvent-Accessible Surface Area SASA (or Total Solvent-Accessible Surface Area, TSASA). Several algorithms were proposed that implement both the first original definition of SASA and that of Richards. One of the most popular algorithms that implements Richards solvent-accessible surface was proposed by Connolly [Connolly, 1983a]. It is an analytical method for computing molecular surface, and is based on surface decomposition into a set of curved regions of spheres and tori that join at circular arcs spheres, tori and arcs are defined by analytical expressions in terms of atomic coordinates, van der Waals radii and the probe radius. Ihe molecular surface calculated in such a way is sometimes referred to as Connolly surface area. This algorithm also allows the calculation of solvent-accessible atomic areas. 

The electrostatic term GENP is accompanied by a second term GCDS which, as the acronym indicates, collects cavitation, dispersion, and solvent structure contributions, the latter regarding dielectric saturation and other reorganization effects, when present. GCDS is modeled in terms of an interfacial atomic surface tension term, <7fc, and of the parameter Ak giving the solvent-accessible surface area for atom k ... 

This is a model for log P calculation based on a group-contribution method proposed by Wang Remdao et al. [Wang, Fu et al, 1997 Wang, Gao et al, 2000]. The model is defined in terms of the solvent accessible surface area and the atomic charges of 76 atom-types, together with five additional correction factors, as... 

The LRA can also be used in an expression for the free energy of solvation in which the components are analogous to those in Eq. (5) for the implicit solvent model by introducing a term proportional to the solvent accessible surface area of the solute [105] ... 

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