Molecular descriptors, QSAR

Key Words Biological activity molecular descriptor QSAR QSPR molecular surface area ... 

Aptula, A.O., Kiihne, R., Ebert, R.-U., Cronin, M.T.D., Netzeva, T.I., and Schuurmann G., Modeling discrimination between antibacterial and non-antibacterial activity based on 3D molecular descriptors, QSAR Combinatorial Sci., 22, 113-128, 2003. 

Grammatica, P. and Papa, E., QSAR modelling of bioconcentration factor by theoretical molecular descriptors, QSAR Comb. Sci., 22, 374-385, 2003. 

Gramatica P, Papa E. An update of the BCF QSAR model based on theoretical molecular descriptors. QSAR Comb Sci 2005 24 953-60. 

The method of building predictive models in QSPR/QSAR can also be applied to the modeling of materials without a unique, clearly defined structure. Instead of the connection table, physicochemical data as well as spectra reflecting the compound s structure can be used as molecular descriptors for model building,... 

Chemoinformatics (or cheminformatics) deals with the storage, retrieval, and analysis of chemical and biological data. Specifically, it involves the development and application of software systems for the management of combinatorial chemical projects, rational design of chemical libraries, and analysis of the obtained chemical and biological data. The major research topics of chemoinformatics involve QSAR and diversity analysis. The researchers should address several important issues. First, chemical structures should be characterized by calculable molecular descriptors that provide quantitative representation of chemical structures. Second, special measures should be developed on the basis of these descriptors in order to quantify structural similarities between pairs of molecules. Finally, adequate computational methods should be established for the efficient sampling of the huge combinatorial structural space of chemical libraries. 

Karelson M. Molecular descriptors in QSAR/QSPR. New York Wiley, 2000. 

Kovatdieva A, Golbraikh A, Oloff S, Feng J, Zheng W, Tropsha A. QSAR modeling of datasets with enantioselective compounds using chirality sensitive molecular descriptors. SAR QSAR Environ Re. 2005 16(l-2) 93-102. 

Duchowicz PR, Castro EA, Toropov AA, Benfenati E (2006) Applications of Flexible Molecular Descriptors in the QSPR-QSAR Study of Heterocyclic Drugs. 3 1-38... 

Bagchi, M. C., Mills, D., Basak, S. C. Quantitative structure-activity relationship (QSAR) studies of quinolone antibacterials against M. fortuitum and M. smegmatis using theoretical molecular descriptors. 

Numerous other QSAR models relating BBB penetration to calculated molecular descriptors have also appeared in literature see for example [27-29]. In each case, PSA was identified as one of the most important parameters determining blood-brain barrier penetration. 

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] ... 

Calculated molecular descriptors including H-bond parameters were used for QSAR studies on different types of permeabiUty. For example, the new H-bond descriptor characterizing the total H-bond ability of a compound, was successfully appUed to model Caco-2 cell permeability of 17 drugs [30]. A similar study on human jejunal in vivo permeabiUty of 22 structurally diverse compounds is described in Ref. [62]. An exceUent one-parameter correlation of human red ceU basal permeabiUty (BP) was obtained using the H-bond donor strength [63] ... 

More typically the process of building up the QSAR models requires more complex chemical information. For a set of compounds, with known property value, the descriptors are calculated. The process of model building proceeds through a reduction of the molecular descriptors, in order to indentify the most important ones. Then, using these selected chemical descriptors and a suitable algorithm, the model is developed. Finally, the model so obtained has to be validated. 

QSAR studies are a fertile area for ANNs and numerous papers have been published in the field. Katritzky s group has a range of interests in this area, particularly related to compounds of biological importance see for example Reference 6. Some QSAR studies have been on a heroic scale. Molnar s group has used training sets of around 13,000 compounds and a total database containing around 30,000 to try to develop meaningful links between cytotoxicity and molecular descriptors.7... 

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. 

Three classes of calculated molecular descriptors, viz., topological and substruc-tural descriptors, geometrical (3-D) indices, and quantum chemical (QC) indices, have been extensively used in QSAR studies pertaining to drug discovery and environmental toxicology [8-12],... 

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