Molecular descriptor electrostatic descriptors

CODESSA can compute or import over 500 molecular descriptors. These can be categorized into constitutional, topological, geometric, electrostatic, quantum chemical, and thermodynamic descriptors. There are automated procedures that will omit missing or bad descriptors. Alternatively, the user can manually define any subset of structures or descriptors to be used. 

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] ... 

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). 

Chemical information can be expressed in a number of ways. Chemical descriptors are commonly used in QSAR. There are thousands of chemical descriptors possibly used in QSAR. Indeed, programs such as DRAGON and CODESSA, just to name a couple, can calculate thousands of parameters [7, 8]. Chemical descriptors have different complexities. Some of them do not require any information on the structure, such as molecular weight. Others refer to the bidimensional structure, such as the number of double bonds. While some others require tridimensional information, such as molecular volume. Chemical descriptors can be geometrical, topological, quantum-mechanical, electrostatical, etc. There are a few books describing chemical descriptors [7, 8],... 

In this context, Hanumantharao et al. [ 129] have carried out a QSAR analysis of the agonist activity of the thiazole derivatives (e) with the molecular descriptors generated from the MOE programme [71]. This has resulted in QSAR models (Eq. 23 and 24) of these compounds in terms of hydropho-bicity of VdW surface areas with different polarities (SlogP, SlogPvsAo and SlogPvsAs). electrostatic potential energy (Eeie). and zero-order connectivity... 

In addition to the steric and electrostatic descriptors, it was proposed to use other 3D molecular fields characterized by the sampling over the rectangular grid - in particular, the hydrophobic field/molecular lipophilic potential (MLP), ° hydrogen bonding and quantum-chemical parameters, e.g., orbital densities.Descriptor selection techniques are often recommended to enhance the stability, predictivity and interpretability of the CoMFA models. ... 

On the basis of the origin of molecular descriptors used in calculations, QSAR methods can be divided into three groups. One group is based on a relatively small number (usually many times smaller than the number of compounds in a data set) of physicochemical properties and parameters describing,for example, hydrophobic, steric, and electrostatic effects. Usually, these descriptors are used as independent variables in multiple regression approaches (18) Jn the literature, these methods are typically referred to as Hansch analysis (8).These types of descriptors and corresponding linear optimization methods used in traditional QSAR analyses are discussed extensively in the chapter by Celassie (7) and therefore is not reviewed here. 

Kroemer, R.T., Hecht, P. and Liedl, K.R. (1996). Different Electrostatic Descriptors in Comparative Molecular Field Analysis A Comparison of Molecular Electrostatic and Coulomb Potentials. J. Comput. Chem., 17,1296-1308. 

The contour parameter m as well as the electrostatic potential can take both positive and negative values. An analysis of the shape of MEP surfaces is of particular interest in —> drug design as the electrostatic potential has a marked influence on the binding interactions between ligand and receptor. Moreover, the sum of all the surface minima values of the electrostatic potential, denoted as proposed as a molecular descriptor able to account for... 

The predictive power, robustness, and reliability of the QSAR/QSPR models depend critically on the use of appropriate molecular descriptors. A myriad of descriptors, either empirical or those calculated on the basis of the molecular structure alone ( theoretical descriptors), have been developed both for the predictive and cognitive purposes [1,2]. Many of those descriptors are based directly on the results of quantum-mechanical calculations or can be derived from the electronic wave function or electrostatic field of the molecule. It is the purpose of the present chapter to give an overview of such molecular descriptors, together with some key applications. 

The calculated total energy of the molecule and its different partitionings can be used as theoretical molecular descriptors. The quantum-chemically calculated total energy of the molecule (/iroi) refers usually to the quantum mechanical standard state for the energy (isolated electrons and nuclei at 0 K). Within the Born Oppenheimer approximation, it can be divided into total electronic energy, Ee, and the nuclear nuclear electrostatic repulsion energy. 

Many molecular properties, especially those measured in condensed media, depend on intermolecular interactions. The main term of such interactions is, in most cases, the electrostatic attraction or repulsion between the molecules or their different parts. Consequently, the respective electrostatic descriptors characterizing a molecule would... 

The quantum-chemical molecular descriptors have been widely used in the development of quantitative structure-activity relationships for various pharmacological activities of compounds. Again, most of the QSARs developed include the electrostatic and/or MO-related descriptors. 

---