Molecular Descriptor Generation

Many thousands of descriptor types have been developed over the years of chemical research. This short review is not intended to summarize these efforts in detail. Todeschini and Consonni have already provided a reference book for this purpose. Commercial and academic software for generating molecular descriptors has proliferated over the recent years. Todeschini s book lists software packages known in the year 2000. Speed of calculation, descriptor quality and diversity should be considered in selecting software. For example, absorption, distribution, metabolism, excretion, toxicity (ADMET) Predictor (Simulations Plus, Inc.) works at a rate of 250,000 molecules per horn calculating 272 molecular and 44 atomic descriptors in the following categories  

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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... 

ADAPT software allows (a) molecular descriptor generation (b) objective feature selection to discard descriptors that contain redundant or minimal information and (c) multiple regression... 

A molecular descriptor generator to encode the structural information of the compounds. We obtained the best results with 2-dimensional fingerprints based on topology of the molecules such as the 2,048-bit default Daylight or 1,024-bit folded Scitegic ECFP 4 descriptors (tee Note 2). 

Multivariate data analysis usually starts with generating a set of spectra and the corresponding chemical structures as a result of a spectrum similarity search in a spectrum database. The peak data are transformed into a set of spectral features and the chemical structures are encoded into molecular descriptors [80]. A spectral feature is a property that can be automatically computed from a mass spectrum. Typical spectral features are the peak intensity at a particular mass/charge value, or logarithmic intensity ratios. The goal of transformation of peak data into spectral features is to obtain descriptors of spectral properties that are more suitable than the original peak list data. 

Because of the large number of chemicals of actual and potential concern, the difficulties and cost of experimental determinations, and scientific interest in elucidating the fundamental molecular determinants of physical-chemical properties, considerable effort has been devoted to generating quantitative structure-property relationships (QSPRs). This concept of structure-property relationships or structure-activity relationships (QSARs) is based on observations of linear free-energy relationships, and usually takes the form of a plot or regression of the property of interest as a function of an appropriate molecular descriptor which can be calculated using only a knowledge of molecular structure or a readily accessible molecular property. 

A major practical issue affecting MP calculations is caused by use of correlated molecular descriptors. During subsequent MP steps, exact halves of values (and molecules) are only generated if the chosen descriptors are uncorrelated (orthogonal), as shown in Fig. 1A. By contrast, the presence of descriptor correlations (and departure from orthogonal reference space) leads to overpopulated and underpopulated, or even empty, partitions (see also Note 5), as illustrated in Fig. ID. For diversity analysis, compounds should be widely distributed over computed partitions and descriptor correlation effects should therefore be limited as much as possible. However, for other applications, the use of correlated descriptors that produce skewed compound distributions may not be problematic or even favorable (see Note 5). 

For pattern-recognition analysis, each compound was initially represented by 896 computer-generated molecular descriptors. Before a descriptor could... 

There are literally thousands of molecular descriptors available for various applications. We have only mentioned a few of them in previous paragraphs. Interested readers can find a more complete coverage of molecular descriptors in reference (15), which gives definitions for 3,300 molecular descriptors. Many software, or subroutines as an integral part of other programs, are available to generate various types of molecular descriptors. Table 2.2 lists a few of these software. 

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