Quantitative structure-activity relationship

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QSAR (quantitative structure-activity relationship, sometimes the A stands also for affinity = reactivity) is the quantitative correlation of the biological (ecological, toxicological or pharmacological) activity to the structure of chemical compounds, which allows the prediction of the so-called "drug efficacy" of a structurally related compound. It is thus closely related to the more general field of QSPR and employs many of the latter's methodology.

The biological activity of molecules is usually measured in assays to establish the level of inhibition of particular signal transduction or metabolic pathways. Chemicals can also be biologically active by being toxic. Drug discovery often involves the use of QSAR to identify chemical structures that could have good inhibitory effects on specific targets and have low toxicity (non-specific activity). Of special interest is the prediction of LogP, which is an important measure used in identifying "drug-likeness" according to Lipinski's Rule of Five.

While many Quantitative Structure Activity Relationship analyses involve the interactions of a family of molecules with an enzyme or receptor binding site, QSAR can also be used to study the interactions between the structural domains of proteins. As in the article Structural modeling extends QSAR analysis of antibody-lysozyme interactions to 3D-QSAR, protein-protein interactions can be quantitatively analyzed for structural variations resulted from site-directed mutagenesis. In this study, a wild-type antibody specific for lysozyme and 17 single and double mutants of the antibody were investigated. Quantitative models for the affinity of the antibody-antigen interaction were developed.

3D-QSAR is a specialization concerned with three-dimensional quantitative structure-activity relationships by methods such as protein crystallography. It uses computers rather than experimental constants and is concerned with the overall molecule rather than a single substituent. It examines the steric fields (shape of the molecule) and the electrostatic fields.

Note: QSAR is pronounced "q-sar" or "quasar".

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