General principles and limitations

The two primary modalities by which crystallography is performed in FBDD are soaking and co-crystallization. In soaking, crystals of generally a very small amount of protein ( j,g amounts) are obtained in solution and either mixtures or single compounds are added at high concentration (25-2(X)mM). After a period of l-24h, the samples are cooled and stored prior to data collection. The hit rate found 

In another example, four fragments (0.12-1.34nM ED50S) were identified that inhibited nucleoside 2-deoxyri-bosyltranserase from Trypanosoma brucei. In this study, 304 fragments were evaluated in 31 mixtures or cocktails. Short soaks of ca. 10 s were sufficient for incorporation of even hydrophobic ligands into the active site groove of this enzyme. 

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This discussion has been aimed solely at qualitative methods that may be applied to unknown components present in a sample at trace levels. Reference should be made to some of the more general principles and limitations of qualitative analysis by GC described in Chapter 4. 

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