Field-based descriptors

Besides the aforementioned descriptors, grid-based methods are frequently used in the field of QSAR quantitative structure-activity relationships) [50]. A molecule is placed in a box and for an orthogonal grid of points the interaction energy values between this molecule and another small molecule, such as water, are calculated. The grid map thus obtained characterizes the molecular shape, charge distribution, and hydrophobicity. 

An additional consideration on the choice of descriptor for diversity analyses is the speed with which the descriptor can be calculated since diversity studies are often applied to the huge numbers of compounds (potentially millions) that characterise combinatorial libraries. Thus, some computationally expensive descriptors such as field-based descriptors [28] or descriptors derived from quantum mechanics [29] are not appropriate for diversity studies. 

A field-based shape descriptor derived from the representation of molecular body by molecular interaction fields and defined as ... 

CoMFA descriptors grid-based QSAR techniques ( Comparative Molecular Field... 

FRAU (Field characterization for Reaction Analysis and Understanding) features encode information about the reaction field of the atoms in a molecule in the three-dimensional space [Satoh, Itono et al, 1999 Satoh, 2007]. These descriptors are based on steric and electrostatic interactions determined by a pseudoreactant. 

Indeed, molecular descriptors are based on several different theories, such as quantum-chemistry, information theory, organic chemistry, graph theory, and so on, and are used to model several different properties of chemicals in scientific fields such as toxicology, analytical chemistry, physical chemistry, and medicinal, pharmaceutical, and environmental chemistry. 

There are several ways in which molecular descriptors can be classified. The majority of descriptors are atom-based rather than field-based. The bulk of this review is focused on a discussion of atom-based descriptors. As the name implies, atom-based descriptors are based on individual atoms, with the description extending outward to incorporate information about the atom s environment. The descriptors are typically generated by analysis of 2D or 3D connection tables, and can include ID, 2D, or 3D information about the molecule. Atom-based descriptors include individual atoms, feature counts, substructural fragments, topological indices, atomic properties, pharmacophores (see Chapters 17 and 18 of this book), and calculated physicochemical properties. 

The descriptors mentioned so far are all essentially atom-based. Some of them represent 3D aspects of molecules, but they do not represent the relative 3D arrangement of the fields responsible for molecular interaction. The alternative is to use field-based descriptors, an area that is receiving increasing interest. A few examples are introduced here. 

The most common method of field-based descriptor generation draws a 3D grid around a molecule and then determines the value of the property of interest (steric, electrostatic, or hydrophobic) at each lattice intersection of the grid. This method originally came from work by Carbo et al. [72] to calculate electron density descriptors, and has been extended by others (e.g., Refs. 73 74 75) to include electrostatic potentials and steric fields. 

Some recent approaches have involved using combinations of 2D and 3D descriptors. For example, BCUT descriptors have been used in combination with four-point pharmacophores [50], and field-based methods have been combined with 2D Daylight fingerprints [47],... 

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. 

Another approach based on statistical analysis of residue-specific protein-ligand interaction terms is named TScore [138[. Here, individual protein-ligand interactions are evaluated for each residue within 8 A around the ligand. Force field-based descriptors are replaced by Chemscore [96] and PLP [139] terms for hydrogen bonds, lipophilicity, and steric contact. Its application to a series of factor Xa inhibitors resulted in a predictive tailored scoring function vdth 52 selected descriptors after PLS analysis q = 0.(>4, r = 0.83). This concept allows a visual interpretation of... 

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