Molecular solvent-accessible

They are the partial positive surface area PPSAi), the total charge weighted positive surface area PPSA2) and the atomic charge weighted positive surface area (PPSAj), divided by the total molecular solvent-accessible surface area (SA-SA), i.e. 

Let SAd and SAa be the solvent accessible surface areas of hydrogen-bonding donors (d) and acceptors (a), respectively, and Qa the corresponding partial atomic charges, SASA the molecular solvent-accessible surface area the HB-CPSA descriptors are then defined as follows (note that the two different symbols encountered in the literature for some are considered as synonymous). 

Depending on the application, models of molecular surfaces arc used to express molecular orbitals, clcaronic densities, van dor Waals radii, or other forms of display. An important definition of a molecular surface was laid down by Richards [182] with the solvent-accessible envelope. Normally the representation is a cloud of points, reticules (meshes or chicken-wire), or solid envelopes. The transparency of solid surfaces may also be indicated (Figure 2-116). 

The following models describe those definitions of molecular surfaces that are most widely used. The van dcr Waals surface, the solvent-accessible surface, and the Connolly surface (sec below) based on Richards definitions play a major role [182],... 

Tn general, the. solvent-accessible surface (SAS) represents a specific class of surfaces, including the Connolly surface. Specifically, the SAS stands for a quite discrete model of a surface, which is based on the work of Lee and Richards [182. They were interested in the interactions between protein and solvent molecules that determine the hydrophobicity and the folding of the proteins. In order to obtain the surface of the molecule, which the solvent can access, a probe sphere rolls over the van der Waals surface (equivalent to the Connolly surface). The trace of the center of the probe sphere determines the solvent-accessible surjace, often called the accessible swface or the Lee and Richards surface (Figure 2-120). Simultaneously, the trajectory generated between the probe and the van der Waals surface is defined as the molecular or Connolly surface. 

Figure 2-120. The center ofthe rolling probe sphere defines the solvent-accessible surface during movement of the probe over the van der Waals surface. Thus, the molecular surface is expanded by the radius of the solvent molecule,...

The MEP at the molecular surface has been used for many QSAR and QSPR applications. Quantum mechanically calculated MEPs are more detailed and accurate at the important areas of the surface than those derived from net atomic charges and are therefore usually preferable [Ij. However, any of the techniques based on MEPs calculated from net atomic charges can be used for full quantum mechanical calculations, and vice versa. The best-known descriptors based on the statistics of the MEP at the molecular surface are those introduced by Murray and Politzer [44]. These were originally formulated for DFT calculations using an isodensity surface. They have also been used very extensively with semi-empirical MO techniques and solvent-accessible surfaces [1, 2]. The charged polar surface area (CPSA) descriptors proposed by Stanton and Jurs [45] are also based on charges derived from semi-empirical MO calculations. 

Richmond T J 1984. Solvent Accessible Surface Area and Excluded Volume in Proteins. Journal oj Molecular Biology 178 63-88. 

In common with similar approaches that relate solvent accessible surface to cavity free energy90-93, the simple SMI model required careful parameterization, and assumed that atoms interacted with solvent in a manner independent of their immediate molecular environment and their hybridization76. In more recent implementations of the SMx approach, ak parameters are selected for particular atoms based on properties determined from the SCF wavefunction that is evaluated during calculation of the solute and solvent polarization energies27. On the other hand, the inclusion of more parameters in the solvation model requires access to substantial amounts of experimental data for the solvation free energies of molecules in the training set94 95. 

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) ... 

Kaznessis et al. [24] Solvent accessible surface area, hydrogen-bonding, solute dipole, molecular volume, etc. 

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