Methods and Examples for Large Library Diversity Calculations

Methods and Examples for Large Library Diversity Calculations 

The age of ultralarge (50000-150000 member) nonpeptide combinatorial libraries [41, 42, 18] is typified by some of the efforts of Merck [43, 44], Pharmacopeia [45], and Houghten Pharmaceuticals [18, 19, 46-48] during the mid-to-late 1990s. While design details often remain unpublished, diversity analyses of several libraries with qualitative comparison to their biological activity exist in the literature [49, 50]. During this era. 

In general, larger libraries, other than those of Pharmacopeia and Houghten, have tended to be in the range of 5000 to 15000 compounds, particularly if the enhre library was purified and stored as individual compounds. The same methods and algorithms as for diverse library design apply here. However, it now becomes possible 

Another approach is the informative library design process, as described by Teig [74]. 

It is a method that samples the chemical space accessible to a library in a manner that, when combined with assay data, allows the elucidation of a set of pharmacophores consistent with biological activity. The library is selected in a manner that maximizes the Shannon entropy [75] for the possible outcomes being tested by the library [76]. 

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