Function-based screening

Greeley J, Nprskov JK. 2007. Large-scale density functional theory-based screening of alloys for hydrogen evolution. Surf Sci 601 1590. 

S. Centi, S. Laschi, M. Franek, and M. Mascini, A disposable immunomagnetic electrochemical sensor based on functionalized magnetic beads and carbon-based screen-printed electrodes (SPCEs) for the detection of polychlorinated biphenyls (PCBs). Anal. Chim. Acta 538, 205—212 (2005). 

Reverse genetic approaches start with a sequence and attempt to identify a function for the gene. This can be done by using PCR-based screens on DNA from insertionally mutagenized populations, ectopic misexpression of the gene, and expression studies, e.g., with RT-PCR or microarray analyses. 

However, if the gene has been cloned, but the required activity is not produced, then the functional test will fail to pick up the target gene. In this case, if some gene sequence information is available, then it may be possible to test for the presence of DNA with the expected sequence by hybridization with radio-labelled probe DNA or, more usually, by PCR. This sequence-based screening test could pick up positives which have been missed in the initial screen because the gene has been successfully cloned but the enzyme has not been produced in an active form (perhaps because expression has not occurred or because E. coli is a poor host to support production of active enzyme), or where there is no convenient function-based assay available. 

As long as the virtual structure-based screening procedure identifies compound proposals that can be realized and tested in a short period of time, the accuracy lacking in the scoring functions can be compensated and finally validated by the biophysical screening experiment itself. 

A.L. Hart and W.A. Collier, Stability and function of screen printed electrodes, based on cholinesterase, stabilised by a co-polymer/sugar alcohol mixture, Sens. Actuators B, 53 (1998) 111-115. 

S. Begle. Chemical function based pharmacophore models as suitable filters for virtual screening. J.Mol. Struct. (THEO-CHEM) 503, 59-72, 2000. 

Generation or use of existing rule-based screens Refinement of known rule-based screens Use of hierarchical models, discriminant functions or decision trees to classify data Generation of QSPkR models (replacing complex or 3D parameters with more rapidly calculable 1D and 2D parameters wherever possible)... 

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