Descriptor electrostatic forces

Comparative molecular Leld analysis (CoMFA) is another promising approach developed in recent years for QSAR study. CoMFA is a molecular modeling technique forthe determination of molecular stericand electrostatic force Lelds (Tripos, 1992). It has been successfully used in deriving molecular descriptors for prediction of the bioactivity of steroids (Cramer etal., 1988), molecular Lux through a polymer membrane (Liu and Matheson, 1994), and metabolism and cytochrome p450 enzyme activities (Long and V felker, 2003). 

It should be noted that, owing to the nature of molecular Leld analysis, there would be hundreds or thousands of descriptors forthe molecular steric and electrostatic force Lelds (Table 3.5), and it is inconvenient and unnecessary to write down the QSSR equation in a CoMFA study since these descriptors are generated and directly used to predict targeted properties using the same software package. Statistical results forthe Lnal models correlating the mole fraction solubility in isopropyl alcohol with the desired parameters for 60 aromatic and heteroaromatic crystalline compounds are... 

H-bonding is an important, but not the sole, interatomic interaction. Thus, total energy is usually calculated as the sum of steric, electrostatic, H-bonding and other components of interatomic interactions. A similar situation holds with QSAR studies of any property (activity) where H-bond parameters are used in combination with other descriptors. For example, five molecular descriptors are applied in the solvation equation of Kamlet-Taft-Abraham excess of molecular refraction (Rj), which models dispersion force interactions arising from the polarizability of n- and n-electrons the solute polarity/polarizability (ir ) due to solute-solvent interactions between bond dipoles and induced dipoles overall or summation H-bond acidity (2a ) overall or summation H-bond basicity (2(3 ) and McGowan volume (VJ [53] ... 

On the other hand, there are several clear perspectives for future improvements and extensions of COSMO-RS. One of the most obvious perspectives is the improvement of the underlying quantum chemical methods. While density functional theory appears to have reached its limit regarding the quality of the electrostatics, and hence of the COSMO polarization charge densities, there will be an increase in the availability of higher correlated ab initio methods like coupled cluster calculations at affordable computational cost. Quantum chemical calculation of local polarizability and eventually of suitable descriptors for dispersion forces should provide additional information about the strength of local surface interactions and can be used to improve the various surface interaction functionals. At the other end, the quantum chemical COSMO calculations for larger biomolecules and enzymes, which have just become available at reasonable... 

The chemical structure representation in Apex-3D is based on the concept of a descriptor center that represents a part of the hypothetical biophore. Descriptor centers can be atoms, sets of atoms, pseudo-atoms, or substructures that participate in ligand-receptor interactions. The interaction is derived from electrostatic, hydrophobic, dispersion force, and charge-transfer information that comes from quantum-chemical calculations or from atomic conkibutions to hydrophobicity or molar refractivity. 

The various properties of molecules that can be used in a QSAR are often designed to quantitate the tendency of the molecules to participate in one of the fundamental types of intermolecular interactions electrostatic, hydrogen bonding, dispersion forces, and hydrophobic interactions. In addition, the possibility of steric interference with an interaction is considered. Other methods capitalize on the fact that the 2D structure of a molecule indirectly encodes its properties, instead generate descriptors without an explicit relationship to some physical property. 

---