Question

Please answer these questions below. Thank you so much!

SMALL MOLECULE LIBRARIES AND SCREENING 17) Explain the difference between forward and reverse chemical genetics in 3 or 4 lines of text? 18) You want to create an inhibitor of the new protease variant (Shredder-V1) you have successfully created. How would you go about designing a library from which you could select or screen for inhibitors that would inhibit Shredder-V1 in vitro. 19) Would you perform the same assay to identify an inhibitor that would act in cells to inhibit Shredder-V1? Explain and suggest, if appropriate, another strategy you could use to identify an inhibitor from a library that could act in cells. 20) What is the Z' value and explain why this parameter is used in high throughput screening efforts. 21) Explain how thermal proteomic profiling works. Describe the basic principle behind why this experiment works.

Answer 1

17) Chemical genetics: Chemical genetics is investigating cellular signal transduction pathways and protein functions by the screening of chemical libraries of small molecules.

Forward chemical genetics: It will identify the pathways and the target genes by studying phenotypes induced by random mutagenesis.

Reverse Chemical genetics: Reverse genetics will begin with a certain gene of interest and will mutate the gene or alter the expression of the gene to identify the phenotype.

20) Z value: Z value is also called as the Z factor. It is a measure of the statistical effect of the size. In high - throughput screens its an attempt to quantify the suitability of a particular assay for use on the full scale.

21) Thermal Proteome Profiling: It is shortly called as the TPP. It measures the heat-induced denaturation of the proteins, Based on the altered thermal stability it will identify the drug bound targets.