True hit

The hit rate within a set of molecules selected by a virtual screen is primarily determined by two parameters the unknown proportion of p hits that exist in the set of molecules scored and the false positive error rate (a) of the classifier used for virtual screening. To a large extent, the statistics of rare events (true hits within a large compound collection) leads to some initially counterintuitive results in the magnitude of a hit rate within a set of molecules selected by a model. 

Wei D et al (2010) Binding energy landscape analysis helps to discriminate true hits from high-scoring decoys in virtual screening. J Chem Inf Model 50(10) 1855-1864... 

All these measures together have greatly increased the proportion of true hits so that, finally, the chemistry capacities are concentrated on fewer but well-characterized hit classes with a clearly increased likeliness of a successful hit-to-lead optimization (Fig. 32.5). 

GPR81 receptor. The red line is the line of unity while the orange line represents the "true hit" cutoff criteria. The dotted line is the straight line fit between the counter and the... 

All of this data supported a conclusion that we were looking at physicochemical compound property behavior or an unspecific assay interference property rather than specific interactions with a given receptor. It was surprising that all three assay technologies against various GPCRs showed a clear response to the compounds with exception of the antagonist screen. The conclusion was that in our hands the pepducin approach would not provide a clear rational approach to identify true hits. 

JSA) Languages, Compilers, and Tools for Embedded Systems (LCTES) ACM Transactions on Embedded Computing Systems (TECS) and International Conference / Workshop on Embedded Software (EMSOFT). These publications have a high number of articles with "embedded system(s)" in their metadata/ Manual inspection of these papers for matches of "reverse engineering" in their metadata did not yield a true hit. 

Effective small molecules are those that increase or decrease the luminescence by >3 standard deviations. Screens should be repeated at least three times. Small molecules that repeatedly cause greater than a threefold change in standard deviation are likely to represent true hits. ... 

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