Quantitative consequence screening modeling

If the slopes of the absorption/time curves differ considerably, a positive hit is indicated (i.e., an enantioselective lipase-variant has been identified) (16). Figure 5 shows two typical experimental plots, illustrating the presence of a non-selective lipase (top) and a hit (bottom) (16). As a consequence of the crudeness of the test, quantitative evaluation is not possible. Therefore, the hits need to be investigated separately in laboratory-scale reactions and evaluated quantitatively by conventional chiral GC. About 800 plots of this kind can easily be recorded per day. A total of 40 000 lipase-variants were generated by epPCR, saturation mutagenesis, cassette mutagenesis, and DNA shuffling and screened in the model reaction. 

Structure-activity relationship (SAR) and, more generally, stracture-property relationship (SPR) analysis are integral to the rational drag design cycle. Quantitative (QSAR, QSPR) methods assume that biological activity is correlated with chemical structures or properties and that as a consequence activity can be modelled as a function of calculable physiochemical attributes. Such a model for activity prediction could then be used, for instance, to screen candidate lead compounds or to suggest directions for new lead molecules. 

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