Screening designs 428 INDEX

We thank Sophia Kossida, Jason Comander, and Yonatan Grad for their helpful suggestions and discussion of the computational screen design and ScanACE and BLAST analysis. The databases used in this work are Flybase (http // www.flybase.org), WormBase (http //www.wormbase.org), and WormPD (http // www.proteome.com/databases/index.hlml). 

Level 3 of the screen is designed to determine the cytotoxic selectivity of samples for tumor cells vs. normal cells. Where possible, the same patient s tissues are used. As in Level 2, six serial dilutions (of four- to five-fold each) are assayed in triplicate for each sample. The diluted samples are then added to the tumor cell and normal cell cultures, and the IC50 is determined. A "selectivity index" (SI) is determined based on the IC50 for normal cells/IC5Q for tumor cells. Samples with an SI of three or more are advanced to Level 4 of the screen. Additionally, only purified and well-characterized compounds are promoted for further testing. 

The program calculates total dissolved solids (TDS), conductivity, and the Langelier and Stiff-Davis Saturation Indexes (see Chapter 3.9). The screen allows the designer to use sodium, calcium, magnesium, chloride, sulfate, or bicarbonate to balance the water analysis. Water quality for up to five feed streams can be entered and blended together to make the total, combined feed water to the system. 

Tanimoto index > 0.9 but may be very different in terms of activity (chemically similar, biologically diverse), while completely different strucmres are known to have the same biological activity (chemically diverse, biologically similar). This intrinsic drawback to the computational screening of virtual libraries should always be considered when interpreting screening results of a computationally designed library, and real data should be used to refine any virtual SAR information based on chemical similarity or dissimilarity. 

For the dioxin binder screening, some changes were made as shown in Fig. 8.6. A new pentapeptide library was prepared because a strong affinity is required, to detect dioxins at the ppb level. The design of the screening solution is very important since it determines which peptides can be screened. Also, the composition of the screening solution may restrict the detection conditions of the sensor. For the herbicide binder screening, ethanol was used to dissolve the herbicide in an aqueous buffer. The refractive index of ethanol (1.3623) is not very different from that of water (1.3335) therefore, the ethanol-based buffer solution could be used in the... 

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