Solvent-accessible surface areas SASA

The solvent accessible surface area (SASA) method is built around the assumption that the greatest amount of interaction with the solvent is in the area very close to the solute molecule. This is accounted for by determining a surface area for each atom or group of atoms that is in contact with the solvent. The free energy of solvation AG° is then computed by... 

In Section III we described an approximation to the nonpolar free energy contribution based on the concept of the solvent-accessible surface area (SASA) [see Eq. (15)]. In the SASA/PB implicit solvent model, the nonpolar free energy contribution is complemented by a macroscopic continuum electrostatic calculation based on the PB equation, thus yielding an approximation to the total free energy, AVP = A different implicit... 

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... 

Predicted solvation free energies and solvent-accessible surface areas (SASA) of 2,4-pentanedione tautomers in cyclohexane and water. a-h... 

Kaznessis et al. [24] used Monte Carlo simulations on a data set of 85 molecules collected from various sources, to calculate physically significant descriptors such as solvent accessible surface area (SASA), solute dipole, number of hydrogen-bond acceptors (HBAC) and donors (HBDN), molecular volume (MVOL), and the hydrophilic, hydrophobic, and amphiphilic components of SASA and related them with BBB permeability using the MLR method. After removing nine strong outliers, the following relationship was developed (Eq. 37) ... 

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). 

The nonpolar (or hydrophobic) component, AGnp may be decomposed into a surface component, which is proportional to the solvent accessible surface area (SASA) of the solute and the component representing the solute-solvent non-electrostatic interactions,57... 

Models for which the parameterizations are based on the solvent accessible surface area (SASA) are widely known in literature.58 The nonpolar component of the free energy of solvation is described in these models as a polynomial of A , where A, is the SASA of the atom i. A very good example of such approach is the Surface Generalized Born/Nonpolar Model (SGB/NP), proposed by Gallicchio and Levy.83 The nonpolar contribution is expressed as ... 

To further characterize the structural changes of goat a-lactalbumin during unfolding, we examined the probability distributions of the following four structural parameters in each of the nine clusters of the structural ensemble of MD trajectories (1) the fractional native contact (Q) of the entire molecule, (2) the RMSD of C atoms between a pair of structures that belong to the same cluster, (3) the solvent-accessible surface area (SASA) of hydrophobic side chains, and (4) the SASA of hydrophilic side chains [25]. 

The choice of exactly what surface area to calculate is, however, not entirely unambiguous. Although one might consider constructing a surface from standard atomic van der Waals radii, the more typical approach is to use the so-called solvent-accessible surface area (SASA)." 23,125 solvent-accessible surface is defined as that generated by the center of a spherical solvent molecule rolling on the van der Waals surface of the solute. A moment s reflection shows that this is the same as the exposed surface obtained by placing spheres at each of the atomic centers, where each sphere has a radius equal to the van der Waals radius of the atom plus the radius of a solvent molecule. For water, which is reasonably well approximated as a spherical solvent, the radius is usually taken as 1.4... 

It is important to emphasize that only the solvent-accessible surface area (SASA), the generalized Born/surface area (GB/SA), and the full AMI—SM2 models purport to address local, nonelectrostatic effects. There is no a priori reason to expect the remaining purely electrostatic models to correlate closely with experiment nevertheless, it is worthwhile to examine the cross-correlations. We will highlight some of the most interesting trends. 

A set of thirty different descriptors [Stanton and Jurs, 1990] which combine shape and electronic information to characterize molecules and therefore encode features responsible for polar interactions between molecules. The molecule representation used for deriving CPSA descriptors views molecule atoms as hard spheres defined by the - van der Waals radius. The - solvent-accessible surface area SASA is used as the molecular surface area it is calculated using a sphere with a radius of 1.5 A to approximate the contact surface formed when a water molecule interacts with the considered molecule. Moreover, the contact surface where polar interactions can take place is characterized by a specific electronic distribution obtained by mapping atomic partial charges on the solvent-accessible surface. 

Model for predicting lipophilicity of compounds based on the -> solvent-accessible surface area SASA generated by a solvent probe of radius 1.4 A and a set of parameters encoding hydrophilic effects of polar groups [Iwaseef al., 1985] ... 

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. 

They are the partial positive surface area PPSAf), the total charge weighted positive surface area PPSA2), and the atomic charge weighted positive surface area (PPSA3), divided by the total molecular solvent-accessible surface area (SASA), that is. 

As a second contribution to the final form of the PP term, we added a part for the solvent-accessible surface area (SASA). Beyond the molecular recognition in terms of preferred distances, the complementarity of shape constitutes an important descriptor for docking. This concept is well defined on considering the surface that is buried between two molecules, after their complexation. For this purpose, we previously developed an efficient way to calculate the SASA of our reduced models [67], and, consequently, of the interface of dimerization. Many articles are concerned with P-P dimers [68] to form stable complexes, the contact surface between two proteins is generally considered to exceed 1200 [69], but additional... 

Solvent water s ability to accommodate a solute s dipolarity appears to be more localized than one might expect. This is somewhat disappointing, because the simple dipole moment is easily available by measurement or calculation. This failure of simple dipole moment is evidenced by the fact that measured log P values for o-dichlorobenzene and p-dichlorobenzene are indistinguishable experimentally (3.43 versus 3.44) while their dipole moments are quite different (2.3D and OD). Note that the difference in solvent-accessible-surface-area (SASA), if pertinent, should also make log P for the ortho isomer appreciably lower (SASA ortho = 2 2.52 para = 285.60). Furthermore, the sequential chlorination of methane gives evidence that it is the localized bond dipoles that lower log P, and that in multiples they may shield each other. See Figure 7.1. 

---