Quantitative structure—activity relationship mechanism

PW91 (Perdew, Wang 1991) a gradient corrected DFT method QCI (quadratic conhguration interaction) a correlated ah initio method QMC (quantum Monte Carlo) an explicitly correlated ah initio method QM/MM a technique in which orbital-based calculations and molecular mechanics calculations are combined into one calculation QSAR (quantitative structure-activity relationship) a technique for computing chemical properties, particularly as applied to biological activity QSPR (quantitative structure-property relationship) a technique for computing chemical properties... 

Quantitative Structure-Activity Relationship studies search for a relationship between the activity/toxicity of chemicals and the numerical representation of their structure and/or features. The overall task is not easy. For instance, several environmental properties are relatively easy to model, but some toxicity endpoints are quite difficult, because the toxicity is the result of many processes, involving different mechanisms. Toxicity data are also affected by experimental errors and their availability is limited because experiments are expensive. A 3D-QSAR model reflects the characteristics of... 

As the chemical models mentioned here refer to some fundamental thermochemical and electronic effects of molecules, their application is not restricted to the prediction of chemical reactivity data. In fact, in the development of the models extensive comparisons were made with physical data, and thus such data can also be predicted from our models. Furthermore, some of the mechanisms responsible for binding substrates to receptors are naturally enough founded on quite similar electronic effects to those responsible for chemical reactivity. This suggest the use of the models developed here to calculate parameters for quantitative structure-activity relationships (QSAR). 

It is not yet possible to design a molecule with specific odor (or taste) characteristics because the relations between sensory properties of flavor compounds and their molecular properties are not well understood. As a consequence, the development of compounds with desired flavor qualities has had to rely on relatively tedious synthetic approaches. Recent advances, however, in computer-based methods developed by the pharmaceutical industry to study QSAR (quantitative structure-activity relationships) may ultimately be helpful in the rational design of new flavor-structures with predictable sensory attributes. Results from QSAR studies may also provide insight into the mechanism of the molecule-receptor interaction. 

Gruber, C. and Buh, V. (1989) Quantum mechanically calculated properties for the development of quantitative structure-activity relationships (QSARs). pfCa values of phenols and aromatic and aliphatic carboxylic acids. Chemosphere, 19, 1595-1609. 

The enormous cost of multiple-species, multiple-dose, lifetime evaluations of chronic effects has already made the task of carrying out hazard assessments of all chemicals in commercial use impossible. At the same time, quantitative structure activity relationship (QSAR) studies are not yet predictive enough to indicate which chemicals should be so tested and which chemicals need not be tested. In exposure assessment, continued development of analytical methods will permit ever more sensitive and selective determinations of toxicants in food and the environment, as well as the effects of chemical mixtures and the potential for interactions that affect the ultimate expression of toxicity. Developments in QSARs, in short-term tests based on the expected mechanism of toxic action and simplification of chronic testing procedures, will all be necessary if the chemicals to which the public and the environment are exposed are to be assessed adequately for their potential to cause harm. 

Quantitative structure/activity relationships (QSARs) for hydrolysis are based on the application of linear free energy relationships (LFERs) (Well, 1968). An LFER is an empirical correlation between the standard free energy of reaction (AG0), or activation energy (Ea) for a series of compounds undergoing the same type of reaction by the same mechanism, and the reaction rate constant. The rate constants vary in a way that molecular descriptors can correlate. 

Woo, Y.T. and Lai, D.Y., Mechanisms of action of chemical carcinogens and their role in structure-activity relationships (SARs) analysis and risk assessment in Quantitative Structure-Activity Relationship (QSAR) Models of Mutagens and Carcinogens, Benigni, R., Ed., CRC Press, Boca Raton, FL 2003, pp. 41-80. 

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